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Primary lymphoedema v3.11 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency 300301 to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Primary lymphoedema v3.10 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from Hennekam lymphangiectasia-lymphedema syndrome, 235510; Hennekam Lymphangiectasia-Lymphedema Syndrome to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510
Primary lymphoedema v3.9 ERG Ivone Leong Phenotypes for gene: ERG were changed from primary lymphoedema to primary lymphoedema, MONDO:0019175
Primary lymphoedema v3.8 ERG Ivone Leong Tag Q4_23_promote_green tag was added to gene: ERG.
Tag Q4_23_NHS_review tag was added to gene: ERG.
Primary lymphoedema v3.8 ERG Ivone Leong Classified gene: ERG as Amber List (moderate evidence)
Primary lymphoedema v3.8 ERG Ivone Leong Added comment: Comment on list classification: New gene submitted by Andrew Mumford (University of Bristol). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. PMID: 36928819 describes 3 families with frameshift variants (2 nonsense-mediated decay variants and 1 protein truncating variant). There is also a fourth family with a protein truncating variant; however, there are other clinical features and lymphoedema was only identified during chart review. Over expression of mutant cDNA caused mislocalisation of ERG in the cytoplasm, preventing it from binding to DNA and functioning as a transcription factor.

Based on the above evidence this gene has been given an Amber gene rating and should be promoted to Green at the next GMS review.
Primary lymphoedema v3.8 ERG Ivone Leong Gene: erg has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v3.7 ERG Ivone Leong Publications for gene: ERG were set to
Primary lymphoedema v3.3 ERG Andrew Mumford gene: ERG was added
gene: ERG was added to Primary lymphoedema. Sources: Research
Mode of inheritance for gene: ERG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ERG were set to primary lymphoedema
Penetrance for gene: ERG were set to Complete
Review for gene: ERG was set to GREEN
Added comment: The association between monoallelic high impact LoF variants in ERG was identified in 4 independent pedigrees in the 100KGP RD main programme and supported by functional evidence of ERG functionality in lymphatic endothelial cells (PMID:36928819)
Sources: Research
Primary lymphoedema v3.3 EPHB4 Arina Puzriakova Phenotypes for gene: EPHB4 were changed from Lymphatic malformation 7 617300 to Lymphatic malformation 7, OMIM:617300
Primary lymphoedema v3.2 PIEZO1 Arina Puzriakova Tag Q4_21_MOI was removed from gene: PIEZO1.
Primary lymphoedema v3.2 PIEZO1 Arina Puzriakova commented on gene: PIEZO1: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed and remains 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.
Primary lymphoedema v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Primary lymphoedema v3.0 Eleanor Williams promoted panel to version 3.0
Primary lymphoedema v2.25 CHD7 Ivone Leong Tag for-review was removed from gene: CHD7.
Primary lymphoedema v2.25 CHD7 Ivone Leong Classified gene: CHD7 as Red List (low evidence)
Primary lymphoedema v2.25 CHD7 Ivone Leong Gene: chd7 has been classified as Red List (Low Evidence).
Primary lymphoedema v2.24 ANGPT2 Ivone Leong Tag for-review was removed from gene: ANGPT2.
Primary lymphoedema v2.24 CHD7 Ivone Leong commented on gene: CHD7: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Primary lymphoedema v2.24 ANGPT2 Ivone Leong commented on gene: ANGPT2: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed.
Primary lymphoedema v2.23 ANGPT2 Sarah Leigh edited their review of gene: ANGPT2: Changed rating: AMBER
Primary lymphoedema v2.23 ANGPT2 Sarah Leigh edited their review of gene: ANGPT2: Added comment: PMID 34876502 reports four fetuses with hydrops fetalis were homozygous for ANGPT2 NM_001147.2:c.557A>G. The consanguiseious parents and surviving sibblings (a girl and a boy), were heterozygous for this variant. This variant is predicted to create a cryptic exonic splice site, resulting in a r.557_566del and nonsense-mediated mRNA decay. This prediction was supported by the lack of a transcript from this allele in the parents.; Changed rating: GREEN; Changed publications to: 34876502; Changed phenotypes to: severe early-onset non-immune hydrops fetalis; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary lymphoedema v2.23 ANGPT2 Sarah Leigh Publications for gene: ANGPT2 were set to 32908006
Primary lymphoedema v2.22 ANGPT2 Sarah Leigh Added comment: Comment on phenotypes: Biallelic variants reported in severe early-onset non-immune hydrops fetalis (PMID 34876502).
Primary lymphoedema v2.22 ANGPT2 Sarah Leigh Phenotypes for gene: ANGPT2 were changed from Lymphatic malformation 10 OMIM:619369; lymphatic malformation 10 MONDO:0023662 to Lymphatic malformation 10 OMIM:619369; lymphatic malformation 10 MONDO:0023662
Primary lymphoedema v2.21 ANGPT2 Sarah Leigh Phenotypes for gene: ANGPT2 were changed from Primary lymphoedema to Lymphatic malformation 10 OMIM:619369; lymphatic malformation 10 MONDO:0023662
Primary lymphoedema v2.20 PIEZO1 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Both mono- and biallelic' to 'Biallelic' only at the next GMS review. Monoallelic variants are associated with hereditary xerocytosis (MIM# 194380), a phenotype that is not relevant to this panel.
Primary lymphoedema v2.20 PIEZO1 Arina Puzriakova Mode of inheritance for gene: PIEZO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary lymphoedema v2.19 PIEZO1 Arina Puzriakova Tag Q4_21_MOI tag was added to gene: PIEZO1.
Primary lymphoedema v2.19 PIEZO1 Arina Puzriakova Phenotypes for gene: PIEZO1 were changed from Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema 194380; Lymphatic malformation 6 616843 to Lymphatic malformation 6, OMIM:616843
Primary lymphoedema v2.18 DCHS1 Arina Puzriakova Phenotypes for gene: DCHS1 were changed from Van Maldergem syndrome 1, 601390 to Van Maldergem syndrome 1, OMIM:601390
Primary lymphoedema v2.17 GJA1 Arina Puzriakova Publications for gene: GJA1 were set to 23550541
Primary lymphoedema v2.16 GJA1 Arina Puzriakova Phenotypes for gene: GJA1 were changed from Oculodentodigital dysplasia 164200 to Oculodentodigital dysplasia, OMIM:164200
Primary lymphoedema v2.15 TIE1 Ivone Leong Tag watchlist tag was added to gene: TIE1.
Primary lymphoedema v2.15 TIE1 Ivone Leong Classified gene: TIE1 as Amber List (moderate evidence)
Primary lymphoedema v2.15 TIE1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. Based on the expert review this gene has been given an Amber rating until more evidence is available.
Primary lymphoedema v2.15 TIE1 Ivone Leong Gene: tie1 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v2.14 TIE1 Ivone Leong Phenotypes for gene: TIE1 were changed from Lymphatic malformation 11, MIM# 619401 to Lymphatic malformation 11, OMIM:619401
Primary lymphoedema v2.13 TIE1 Zornitza Stark gene: TIE1 was added
gene: TIE1 was added to Primary lymphoedema. Sources: Literature
Mode of inheritance for gene: TIE1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TIE1 were set to 32947856; 24764452
Phenotypes for gene: TIE1 were set to Lymphatic malformation 11, MIM# 619401
Review for gene: TIE1 was set to AMBER
Added comment: Three families reported, supportive animal model, though variants are missense and present at a low frequency in gnomad, hence Amber rating suggested.
Sources: Literature
Primary lymphoedema v2.13 CELSR1 Arina Puzriakova Phenotypes for gene: CELSR1 were changed from hereditary lymphedema to Lymphatic malformation 9, OMIM:619319
Primary lymphoedema v2.12 ARAP3 Ivone Leong Classified gene: ARAP3 as Amber List (moderate evidence)
Primary lymphoedema v2.12 ARAP3 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Primary lymphoedema v2.12 ARAP3 Ivone Leong Gene: arap3 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v2.11 ARAP3 Ivone Leong Tag watchlist tag was added to gene: ARAP3.
Primary lymphoedema v2.11 RORC Ivone Leong Classified gene: RORC as Amber List (moderate evidence)
Primary lymphoedema v2.11 RORC Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been rated Amber.
Primary lymphoedema v2.11 RORC Ivone Leong Gene: rorc has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v2.10 RORC Ivone Leong Tag watchlist tag was added to gene: RORC.
Primary lymphoedema v2.10 RORC Ivone Leong Phenotypes for gene: RORC were changed from Lymphoedema to Lymphoedema, MONDO:0019297
Primary lymphoedema v2.9 ARAP3 Ivone Leong Phenotypes for gene: ARAP3 were changed from Lymphoedema to Lymphoedema, MONDO:0019297
Primary lymphoedema v2.8 RORC Zornitza Stark gene: RORC was added
gene: RORC was added to Primary lymphoedema. Sources: Literature
Mode of inheritance for gene: RORC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RORC were set to 32960152
Phenotypes for gene: RORC were set to Lymphoedema
Review for gene: RORC was set to AMBER
Added comment: Two individuals reported with LoF variants as part of a large cohort. Note gene is depleted for LoF in gnomad, and bi-allelic variants have been associated with immunodeficiency. Moderate/limited evidence for gene-disease association.
Sources: Literature
Primary lymphoedema v2.8 ARAP3 Zornitza Stark gene: ARAP3 was added
gene: ARAP3 was added to Primary lymphoedema. Sources: Literature
Mode of inheritance for gene: ARAP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARAP3 were set to 32908855
Phenotypes for gene: ARAP3 were set to Lymphoedema
Review for gene: ARAP3 was set to AMBER
Added comment: Three unrelated families reported with rare missense variants in this gene as part of a lymphoedema cohort. However, incomplete information regarding segregation and no supporting functional data.
Sources: Literature
Primary lymphoedema v2.8 ADAMTS3 Arina Puzriakova Phenotypes for gene: ADAMTS3 were changed from Hennekam syndrome; Hennekam lymphangiectasia-lymphedema syndrome 3 to Hennekam lymphangiectasia-lymphedema syndrome 3, OMIM:618154; Hennekam lymphangiectasia-lymphedema syndrome 3, MONDO:0032564
Primary lymphoedema v2.7 MPI Arina Puzriakova Phenotypes for gene: MPI were changed from to Congenital disorder of glycosylation, type Ib, OMIM:602579; MPI-CDG, MONDO:0011257
Primary lymphoedema v2.6 ANGPT2 Ivone Leong Tag for-review tag was added to gene: ANGPT2.
Primary lymphoedema v2.6 ANGPT2 Ivone Leong Classified gene: ANGPT2 as Amber List (moderate evidence)
Primary lymphoedema v2.6 ANGPT2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark. There is enough evidence for this gene to be rated Green, which will occur at the next major review/update.
Primary lymphoedema v2.6 ANGPT2 Ivone Leong Gene: angpt2 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v2.5 FBXL7 Ivone Leong Classified gene: FBXL7 as Red List (low evidence)
Primary lymphoedema v2.5 FBXL7 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark. There is only 1 case and therefore not enough evidence to support a gene-disease association.
Primary lymphoedema v2.5 FBXL7 Ivone Leong Gene: fbxl7 has been classified as Red List (Low Evidence).
Primary lymphoedema v2.4 ANGPT2 Zornitza Stark gene: ANGPT2 was added
gene: ANGPT2 was added to Primary lymphoedema. Sources: Literature
Mode of inheritance for gene: ANGPT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANGPT2 were set to 32908006
Phenotypes for gene: ANGPT2 were set to Primary lymphoedema
Review for gene: ANGPT2 was set to GREEN
Added comment: Five unrelated individuals reported with primary lymphedema and variants in this gene, together with functional data.
Sources: Literature
Primary lymphoedema v2.4 FBXL7 Zornitza Stark gene: FBXL7 was added
gene: FBXL7 was added to Primary lymphoedema. Sources: Literature
Mode of inheritance for gene: FBXL7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBXL7 were set to 31633297
Phenotypes for gene: FBXL7 were set to Hennekam syndrome; lymphoedema
Review for gene: FBXL7 was set to RED
Added comment: Homozygous deletion of exon 3 of FBXL7 (predicted to be in-frame) in a 2-year old with novel form of Hennekam syndrome. Each parent was heterozygous.
Patient had lymphedema, protein‐losing enteropathy, dental anomalies, camptodactyly, microtia, small auditory canals, ductive hearing loss, middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae.
Sources: Literature
Primary lymphoedema v2.4 CHD7 Ivone Leong reviewed gene: CHD7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary lymphoedema v2.4 CHD7 Ivone Leong Tag for-review tag was added to gene: CHD7.
Primary lymphoedema v2.4 CHD7 Zornitza Stark reviewed gene: CHD7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: CHARGE syndrome, MIM# 214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary lymphoedema v2.3 Catherine Snow Panel version has been signed off
Primary lymphoedema v2.0 PTPN14 Louise Daugherty commented on gene: PTPN14
Primary lymphoedema v2.0 Ivone Leong promoted panel to version 2.0
Primary lymphoedema v1.123 Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off
Primary lymphoedema v1.122 Ivone Leong List of related panels changed from Lymphatic Disorders; Meiges disease; Meige disease; Milroy disease; Lymphoedema distichiasis; Lipoedema disease to Lymphatic Disorders; Meiges disease; Meige disease; Milroy disease; Lymphoedema distichiasis; Lipoedema disease; R136
Primary lymphoedema v1.121 SHANK3 Ivone Leong Phenotypes for gene: SHANK3 were changed from to Phelan-McDermid syndrome 606232
Primary lymphoedema v1.120 PMM2 Ivone Leong Phenotypes for gene: PMM2 were changed from to Congenital disorder of glycosylation, type Ia 212065
Primary lymphoedema v1.119 TSC2 Ivone Leong Phenotypes for gene: TSC2 were changed from to ?Focal cortical dysplasia, type II, somatic 607341; Lymphangioleiomyomatosis, somatic 606690; Tuberous sclerosis-2 613254
Primary lymphoedema v1.118 TSC1 Ivone Leong Phenotypes for gene: TSC1 were changed from to Focal cortical dysplasia, type II, somatic 607341; Lymphangioleiomyomatosis 606690; Tuberous sclerosis-1 191100
Primary lymphoedema v1.117 TSC1 Ivone Leong Classified gene: TSC1 as Green List (high evidence)
Primary lymphoedema v1.117 TSC1 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. After discussion with the Clinical Team (Genomics England), it was decided that this gene should be promoted to Green status based on the expert opinion of Professor Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.117 TSC1 Ivone Leong Gene: tsc1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.116 TSC2 Ivone Leong Classified gene: TSC2 as Green List (high evidence)
Primary lymphoedema v1.116 TSC2 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. After discussion with the Clinical Team (Genomics England), it was decided that this gene should be promoted to Green status based on the expert opinion of Professor Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.116 TSC2 Ivone Leong Gene: tsc2 has been classified as Green List (High Evidence).
Primary lymphoedema v1.115 NSD1 Ivone Leong Classified gene: NSD1 as Green List (high evidence)
Primary lymphoedema v1.115 NSD1 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. After discussion with the Clinical Team (Genomics England), it was decided that this gene should be promoted to Green status based on the expert opinion of Professor Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.115 NSD1 Ivone Leong Gene: nsd1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.114 RASA1 Ivone Leong Classified gene: RASA1 as Green List (high evidence)
Primary lymphoedema v1.114 RASA1 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. After discussion with the Clinical Team (Genomics England), it was decided that this gene should be promoted to Green status based on the expert opinion of Professor Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.114 RASA1 Ivone Leong Gene: rasa1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.113 DCHS1 Ellen McDonagh Marked gene: DCHS1 as ready
Primary lymphoedema v1.113 DCHS1 Ellen McDonagh Gene: dchs1 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v1.113 TSC2 Sarah Leigh Classified gene: TSC2 as Amber List (moderate evidence)
Primary lymphoedema v1.113 TSC2 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Prof Sahar Mansour (St George's Hospital, London) lymphoedema has been reported with tuberous sclerosis once or twice in the literature and we have a couple of patients but it is rare and there are usually other clues to the diagnosis.
Primary lymphoedema v1.113 TSC2 Sarah Leigh Gene: tsc2 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v1.112 TSC1 Sarah Leigh Classified gene: TSC1 as Amber List (moderate evidence)
Primary lymphoedema v1.112 TSC1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Prof Sahar Mansour (St George's Hospital, London) lymphoedema has been reported with tuberous sclerosis once or twice in the literature and we have a couple of patients but it is rare and there are usually other clues to the diagnosis.
Primary lymphoedema v1.112 TSC1 Sarah Leigh Gene: tsc1 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v1.111 NSD1 Sarah Leigh Classified gene: NSD1 as Amber List (moderate evidence)
Primary lymphoedema v1.111 NSD1 Sarah Leigh Added comment: Comment on list classification: According to Prof Sahar Mansour (St Georges Hospital, London), lymphoedema has been reported in some cases of Sotos syndrome 1 117550.
Primary lymphoedema v1.111 NSD1 Sarah Leigh Gene: nsd1 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v1.110 NSD1 Sarah Leigh Phenotypes for gene: NSD1 were changed from to Sotos syndrome 1 117550
Primary lymphoedema v1.109 NSD1 Sarah Leigh Publications for gene: NSD1 were set to 9781911
Primary lymphoedema v1.108 RASA1 Sarah Leigh changed review comment from: Comment on list classification: From Gene Reviews (https://www.ncbi.nlm.nih.gov/books/NBK52764/) "Lymphatic malformations have been reported in several individuals [de Wijn et al 2012, Burrows et al 2013, Macmurdo et al 2016], including one individual with RASA1-related Parkes Weber syndrome. Lymphangiography and near-infrared fluorescence lymphatic imaging showed abnormally dilated collecting lymphatics with sluggish flow in the unaffected limb, and tortuous lymphatics of the affected limb with lymphocele-like vesicles on the groin [Burrows et al 2013]. Whether these lymphatic abnormalities are progressive is not yet known."; to: Comment on list classification: From Gene Reviews (https://www.ncbi.nlm.nih.gov/books/NBK52764/) "Lymphatic malformations have been reported in several individuals [PMIDs 26969842, 23650393, 22342634], including one individual with RASA1-related Parkes Weber syndrome. Lymphangiography and near-infrared fluorescence lymphatic imaging showed abnormally dilated collecting lymphatics with sluggish flow in the unaffected limb, and tortuous lymphatics of the affected limb with lymphocele-like vesicles on the groin [PMID 23650393]. Whether these lymphatic abnormalities are progressive is not yet known."
Primary lymphoedema v1.108 RASA1 Sarah Leigh Classified gene: RASA1 as Amber List (moderate evidence)
Primary lymphoedema v1.108 RASA1 Sarah Leigh Added comment: Comment on list classification: From Gene Reviews (https://www.ncbi.nlm.nih.gov/books/NBK52764/) "Lymphatic malformations have been reported in several individuals [de Wijn et al 2012, Burrows et al 2013, Macmurdo et al 2016], including one individual with RASA1-related Parkes Weber syndrome. Lymphangiography and near-infrared fluorescence lymphatic imaging showed abnormally dilated collecting lymphatics with sluggish flow in the unaffected limb, and tortuous lymphatics of the affected limb with lymphocele-like vesicles on the groin [Burrows et al 2013]. Whether these lymphatic abnormalities are progressive is not yet known."
Primary lymphoedema v1.108 RASA1 Sarah Leigh Gene: rasa1 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v1.107 RASA1 Sarah Leigh Publications for gene: RASA1 were set to
Primary lymphoedema v1.106 RASA1 Sarah Leigh Phenotypes for gene: RASA1 were changed from to Capillary malformation-arteriovenous malformation 1 608354
Primary lymphoedema v1.105 MPI Sarah Leigh changed review comment from: PMI is old gene name (15q24.1-.2) is associated with Congenital disorder of glycosylation, type Ib 602579, which includes lymphangiectasia. The gene submitted on expert list was PM1 (new gene name TMEM11 (17p11.1), this is not on OMIM and not associated with condition on G2P).; to: PMI is old gene name (15q24.1-.2) is associated with Congenital disorder of glycosylation, type Ib 602579, which includes lymphangiectasia. The gene submitted on expert list was PM1 (new gene name TMEM11 (17p11.1), this is not on OMIM and not associated with a condition on G2P).
Primary lymphoedema v1.105 MPI Sarah Leigh changed review comment from: PMI is old gene name ( 15q24.1-.2) is associated with Congenital disorder of glycosylation, type Ib 602579, which includes lymphangiectasia. The gene submitted on expert list was PM1 (new gene name TMEM11 (17p11.1), this is not on OMIM and not associated with condition on G2P).; to: PMI is old gene name (15q24.1-.2) is associated with Congenital disorder of glycosylation, type Ib 602579, which includes lymphangiectasia. The gene submitted on expert list was PM1 (new gene name TMEM11 (17p11.1), this is not on OMIM and not associated with condition on G2P).
Primary lymphoedema v1.105 CELSR1 Sarah Leigh Penetrance for gene CELSR1 was set from to None
Primary lymphoedema v1.104 CELSR1 Sarah Leigh Classified gene: CELSR1 as Green List (high evidence)
Primary lymphoedema v1.104 CELSR1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 7 variants reported, showing incomplete penetrance, whereby male carries did not manifest with lymphoedema except in later life (PMID 31215153).
Primary lymphoedema v1.104 CELSR1 Sarah Leigh Gene: celsr1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.103 CELSR1 Sarah Leigh gene: CELSR1 was added
gene: CELSR1 was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: CELSR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CELSR1 were set to 31403174; 26855770; 31215153
Phenotypes for gene: CELSR1 were set to hereditary lymphedema
Review for gene: CELSR1 was set to GREEN
Added comment: Sources: Expert list
Primary lymphoedema v1.102 CHD7 Sarah Leigh Publications for gene: CHD7 were set to
Primary lymphoedema v1.101 CHD7 Sarah Leigh Added comment: Comment on phenotypes: Variants are also associated with Hypogonadotropic hypogonadism 5 with or without anosmia 612370, but this is not relevant to this panel.
Primary lymphoedema v1.101 CHD7 Sarah Leigh Phenotypes for gene: CHD7 were changed from CHARGE syndrome 214800 to CHARGE syndrome 214800
Primary lymphoedema v1.100 CHD7 Sarah Leigh Classified gene: CHD7 as Green List (high evidence)
Primary lymphoedema v1.100 CHD7 Sarah Leigh Gene: chd7 has been classified as Green List (High Evidence).
Primary lymphoedema v1.99 CHD7 Sarah Leigh gene: CHD7 was added
gene: CHD7 was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CHD7 were set to CHARGE syndrome 214800
Review for gene: CHD7 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for CHARGE syndrome 214800. At least 14 variants reported associated with CHARGE syndrome 214800.
Sources: Expert list
Primary lymphoedema v1.98 Sarah Leigh removed gene:CDH7 from the panel
Primary lymphoedema v1.97 PMM2 Sarah Leigh Classified gene: PMM2 as Green List (high evidence)
Primary lymphoedema v1.97 PMM2 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London), together with association with relevant phenotype and sufficient variants reported.
Primary lymphoedema v1.97 PMM2 Sarah Leigh Gene: pmm2 has been classified as Green List (High Evidence).
Primary lymphoedema v1.96 SHANK3 Sarah Leigh Classified gene: SHANK3 as Green List (high evidence)
Primary lymphoedema v1.96 SHANK3 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London), together with association with relevant phenotype and sufficient variants reported.
Primary lymphoedema v1.96 SHANK3 Sarah Leigh Gene: shank3 has been classified as Green List (High Evidence).
Primary lymphoedema v1.95 HGF Sarah Leigh Publications for gene: HGF were set to
Primary lymphoedema v1.94 MET Sarah Leigh Publications for gene: MET were set to
Primary lymphoedema v1.93 VEGFC Sarah Leigh Publications for gene: VEGFC were set to 23410910; 24744435; 14634646
Primary lymphoedema v1.92 NSD1 Sarah Leigh Publications for gene: NSD1 were set to
Primary lymphoedema v1.91 ALG8 Sarah Leigh Publications for gene: ALG8 were set to
Primary lymphoedema v1.90 PMM2 Sarah Leigh Publications for gene: PMM2 were set to
Primary lymphoedema v1.89 CDH7 Sarah Leigh Publications for gene: CDH7 were set to
Primary lymphoedema v1.88 HGF Sahar Mansour reviewed gene: HGF: Rating: RED; Mode of pathogenicity: ; Publications: 18564920; Phenotypes: Primary and Secondary Lymphedema; Mode of inheritance: Unknown
Primary lymphoedema v1.88 MET Sahar Mansour reviewed gene: MET: Rating: RED; Mode of pathogenicity: ; Publications: 18564920; Phenotypes: Primary and Secondary Lymphedema; Mode of inheritance: Unknown
Primary lymphoedema v1.88 ADAMTS3 Sahar Mansour reviewed gene: ADAMTS3: Rating: GREEN; Mode of pathogenicity: ; Publications: 28985353, 30450763; Phenotypes: Hennekam lymphangiectasia-lymphedema syndrome 3 618154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary lymphoedema v1.88 IKBKG Sahar Mansour reviewed gene: IKBKG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency 300301; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Primary lymphoedema v1.88 VEGFC Sahar Mansour reviewed gene: VEGFC: Rating: GREEN; Mode of pathogenicity: ; Publications: 30071673, 23410910; Phenotypes: Congenital Primary Lymphoedema of Gordon, Lymphatic malformation 4 615907; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.88 PIEZO1 Sahar Mansour reviewed gene: PIEZO1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema 194380, Lymphatic malformation 6 616843; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary lymphoedema v1.88 EPHB4 Sahar Mansour reviewed gene: EPHB4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Capillary malformation-arteriovenous malformation 2 618196, Lymphatic malformation 7 617300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.88 NSD1 Sarah Leigh reviewed gene: NSD1: Rating: RED; Mode of pathogenicity: ; Publications: 9781911; Phenotypes: Sotos syndrome 1 117550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.88 RASA1 Sarah Leigh reviewed gene: RASA1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Capillary malformation-arteriovenous malformation 1 608354; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.88 ALG8 Sarah Leigh reviewed gene: ALG8: Rating: RED; Mode of pathogenicity: ; Publications: 12480927, 15235028; Phenotypes: Congenital disorder of glycosylation, type Ih 608104; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary lymphoedema v1.88 MPI Sarah Leigh reviewed gene: MPI: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ib 602579; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary lymphoedema v1.88 PMM2 Sarah Leigh reviewed gene: PMM2: Rating: GREEN; Mode of pathogenicity: ; Publications: 17158594, 9762608, 15645285, 20638314; Phenotypes: Congenital disorder of glycosylation, type Ia 212065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary lymphoedema v1.88 TSC2 Sarah Leigh reviewed gene: TSC2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ?Focal cortical dysplasia, type II, somatic 607341, Lymphangioleiomyomatosis, somatic 606690, Tuberous sclerosis-2 613254; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.88 TSC1 Sarah Leigh reviewed gene: TSC1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Focal cortical dysplasia, type II, somatic 607341, Lymphangioleiomyomatosis 606690, Tuberous sclerosis-1 191100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.88 CDH7 Sarah Leigh reviewed gene: CDH7: Rating: RED; Mode of pathogenicity: ; Publications: 22765916, 24554215; Phenotypes: ; Mode of inheritance: Unknown
Primary lymphoedema v1.88 SHANK3 Sarah Leigh reviewed gene: SHANK3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Phelan-McDermid syndrome 606232; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.87 MET Sarah Leigh commented on gene: MET
Primary lymphoedema v1.87 HGF Sarah Leigh commented on gene: HGF
Primary lymphoedema v1.87 HGF Sarah Leigh Mode of inheritance for gene: HGF was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to Unknown
Primary lymphoedema v1.86 ADAMTS3 Sarah Leigh changed review comment from: Comment on list classification: Associate with phenotype in OMIM, but not in Gen2Phen. Three variants in two cases, together with supportive functional studies (PMID 30450763).; to: Comment on list classification: Associate with phenotype in OMIM, but not in Gen2Phen. At lease three variants in two cases, together with supportive functional studies (PMID 30450763).
Primary lymphoedema v1.86 ADAMTS3 Sarah Leigh Publications for gene: ADAMTS3 were set to 28985353; 28687807; 26446156
Primary lymphoedema v1.85 ADAMTS3 Sarah Leigh Tag watchlist was removed from gene: ADAMTS3.
Primary lymphoedema v1.85 ADAMTS3 Sarah Leigh Classified gene: ADAMTS3 as Green List (high evidence)
Primary lymphoedema v1.85 ADAMTS3 Sarah Leigh Added comment: Comment on list classification: Associate with phenotype in OMIM, but not in Gen2Phen. Three variants in two cases, together with supportive functional studies (PMID 30450763).
Primary lymphoedema v1.85 ADAMTS3 Sarah Leigh Gene: adamts3 has been classified as Green List (High Evidence).
Primary lymphoedema v1.84 IKBKG Sarah Leigh changed review comment from: Comment when marking as ready: Associated with phenotype in OMIM and as a confirmed Developmental Disorder Gene / G2P. ; to: Comment when marking as ready: Associated with phenotype in OMIM and as a confirmed Developmental Disorder Gene / G2P. At least 2 variants reported in 3 cases.
Primary lymphoedema v1.84 IKBKG Sarah Leigh changed review comment from: Comment when marking as ready: Associated with phenotype in OMIM and as a confirmed Developmental Disorder Gene / G2P. ; to: Comment when marking as ready: Associated with phenotype in OMIM and as a confirmed Developmental Disorder Gene / G2P.
Primary lymphoedema v1.84 PIEZO1 Sarah Leigh changed review comment from: Comment when marking as ready: Associated with phenotype in OMIM, not in G2P / DD. At least 7 variants reported; to: Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 7 variants reported in Lymphatic malformation 6 616843
Primary lymphoedema v1.84 PIEZO1 Sarah Leigh Deleted their comment
Primary lymphoedema v1.84 PIEZO1 Sarah Leigh Added comment: Comment on phenotypes: Lymphatic malformation 6 616843 was previously known as Lymphedema, hereditary, III 616843
Primary lymphoedema v1.84 PIEZO1 Sarah Leigh Phenotypes for gene: PIEZO1 were changed from Lymphedema, hereditary, III 616843; Generalised lymphatic dysplasia to Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema 194380; Lymphatic malformation 6 616843
Primary lymphoedema v1.83 HGF Sarah Leigh gene: HGF was added
gene: HGF was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: HGF was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary lymphoedema v1.83 MET Sarah Leigh gene: MET was added
gene: MET was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: MET was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary lymphoedema v1.83 ADAMTS3 Sarah Leigh Source Expert list was added to ADAMTS3.
Primary lymphoedema v1.83 IKBKG Sarah Leigh Source Expert list was added to IKBKG.
Primary lymphoedema v1.83 VEGFC Sarah Leigh Mode of inheritance for gene VEGFC was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.83 PIEZO1 Sarah Leigh Mode of inheritance for gene PIEZO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary lymphoedema v1.83 EPHB4 Sarah Leigh Mode of inheritance for gene EPHB4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.83 NSD1 Sarah Leigh gene: NSD1 was added
gene: NSD1 was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: NSD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.83 RASA1 Sarah Leigh gene: RASA1 was added
gene: RASA1 was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: RASA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.83 ALG8 Sarah Leigh gene: ALG8 was added
gene: ALG8 was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: ALG8 was set to BIALLELIC, autosomal or pseudoautosomal
Primary lymphoedema v1.83 MPI Sarah Leigh gene: MPI was added
gene: MPI was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: MPI was set to BIALLELIC, autosomal or pseudoautosomal
Primary lymphoedema v1.83 PMM2 Sarah Leigh gene: PMM2 was added
gene: PMM2 was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Primary lymphoedema v1.83 TSC2 Sarah Leigh gene: TSC2 was added
gene: TSC2 was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: TSC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.83 TSC1 Sarah Leigh gene: TSC1 was added
gene: TSC1 was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: TSC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.83 CDH7 Sarah Leigh gene: CDH7 was added
gene: CDH7 was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: CDH7 was set to
Primary lymphoedema v1.83 SHANK3 Sarah Leigh gene: SHANK3 was added
gene: SHANK3 was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: SHANK3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.82 TTR Ellen McDonagh Publications for gene: TTR were set to
Primary lymphoedema v1.81 TTR Ellen McDonagh reviewed gene: TTR: Rating: ; Mode of pathogenicity: None; Publications: 30878017, 31131842, 31118583, 31111153, 30120737; Phenotypes: Amyloidosis, hereditary, transthyretin-related 105210; Mode of inheritance: None
Primary lymphoedema v1.81 TTR Ellen McDonagh Tag treatable tag was added to gene: TTR.
Primary lymphoedema v1.81 SPRED1 Sarah Leigh Publications for gene: SPRED1 were set to
Primary lymphoedema v1.80 SPRED1 Sarah Leigh Classified gene: SPRED1 as Green List (high evidence)
Primary lymphoedema v1.80 SPRED1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.80 SPRED1 Sarah Leigh Gene: spred1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.79 SOS2 Sarah Leigh Publications for gene: SOS2 were set to
Primary lymphoedema v1.78 SOS2 Sarah Leigh Classified gene: SOS2 as Green List (high evidence)
Primary lymphoedema v1.78 SOS2 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.78 SOS2 Sarah Leigh Gene: sos2 has been classified as Green List (High Evidence).
Primary lymphoedema v1.77 SOS1 Sarah Leigh Publications for gene: SOS1 were set to
Primary lymphoedema v1.76 SOS1 Sarah Leigh Classified gene: SOS1 as Green List (high evidence)
Primary lymphoedema v1.76 SOS1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.76 SOS1 Sarah Leigh Gene: sos1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.75 SHOC2 Sarah Leigh Publications for gene: SHOC2 were set to
Primary lymphoedema v1.74 SHOC2 Sarah Leigh Classified gene: SHOC2 as Green List (high evidence)
Primary lymphoedema v1.74 SHOC2 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.74 SHOC2 Sarah Leigh Gene: shoc2 has been classified as Green List (High Evidence).
Primary lymphoedema v1.73 RIT1 Sarah Leigh Publications for gene: RIT1 were set to
Primary lymphoedema v1.72 RIT1 Sarah Leigh Classified gene: RIT1 as Green List (high evidence)
Primary lymphoedema v1.72 RIT1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.72 RIT1 Sarah Leigh Gene: rit1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.71 RAF1 Sarah Leigh Publications for gene: RAF1 were set to
Primary lymphoedema v1.70 RAF1 Sarah Leigh Classified gene: RAF1 as Green List (high evidence)
Primary lymphoedema v1.70 RAF1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.70 RAF1 Sarah Leigh Gene: raf1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.69 PTPN11 Sarah Leigh Publications for gene: PTPN11 were set to
Primary lymphoedema v1.68 PTPN11 Sarah Leigh Classified gene: PTPN11 as Green List (high evidence)
Primary lymphoedema v1.68 PTPN11 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.68 PTPN11 Sarah Leigh Gene: ptpn11 has been classified as Green List (High Evidence).
Primary lymphoedema v1.67 PPP1CB Sarah Leigh Publications for gene: PPP1CB were set to
Primary lymphoedema v1.66 PPP1CB Sarah Leigh Classified gene: PPP1CB as Green List (high evidence)
Primary lymphoedema v1.66 PPP1CB Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.66 PPP1CB Sarah Leigh Gene: ppp1cb has been classified as Green List (High Evidence).
Primary lymphoedema v1.65 NRAS Sarah Leigh Publications for gene: NRAS were set to
Primary lymphoedema v1.64 NRAS Sarah Leigh Classified gene: NRAS as Green List (high evidence)
Primary lymphoedema v1.64 NRAS Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.64 NRAS Sarah Leigh Gene: nras has been classified as Green List (High Evidence).
Primary lymphoedema v1.63 NF1 Sarah Leigh Classified gene: NF1 as Green List (high evidence)
Primary lymphoedema v1.63 NF1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.63 NF1 Sarah Leigh Gene: nf1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.62 NF1 Sarah Leigh Publications for gene: NF1 were set to
Primary lymphoedema v1.61 NF1 Sarah Leigh Classified gene: NF1 as Green List (high evidence)
Primary lymphoedema v1.61 NF1 Sarah Leigh Gene: nf1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.60 MAP2K2 Sarah Leigh Publications for gene: MAP2K2 were set to
Primary lymphoedema v1.59 MAP2K2 Sarah Leigh Classified gene: MAP2K2 as Green List (high evidence)
Primary lymphoedema v1.59 MAP2K2 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.59 MAP2K2 Sarah Leigh Gene: map2k2 has been classified as Green List (High Evidence).
Primary lymphoedema v1.58 MAP2K1 Sarah Leigh Publications for gene: MAP2K1 were set to
Primary lymphoedema v1.57 MAP2K1 Sarah Leigh Classified gene: MAP2K1 as Green List (high evidence)
Primary lymphoedema v1.57 MAP2K1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.57 MAP2K1 Sarah Leigh Gene: map2k1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.56 LZTR1 Sarah Leigh Publications for gene: LZTR1 were set to
Primary lymphoedema v1.55 LZTR1 Sarah Leigh Classified gene: LZTR1 as Green List (high evidence)
Primary lymphoedema v1.55 LZTR1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.55 LZTR1 Sarah Leigh Gene: lztr1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.54 KRAS Sarah Leigh Publications for gene: KRAS were set to
Primary lymphoedema v1.53 KRAS Sarah Leigh Classified gene: KRAS as Green List (high evidence)
Primary lymphoedema v1.53 KRAS Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.53 KRAS Sarah Leigh Gene: kras has been classified as Green List (High Evidence).
Primary lymphoedema v1.52 HRAS Sarah Leigh Publications for gene: HRAS were set to
Primary lymphoedema v1.51 HRAS Sarah Leigh Classified gene: HRAS as Green List (high evidence)
Primary lymphoedema v1.51 HRAS Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.51 HRAS Sarah Leigh Gene: hras has been classified as Green List (High Evidence).
Primary lymphoedema v1.50 CBL Sarah Leigh Classified gene: CBL as Green List (high evidence)
Primary lymphoedema v1.50 CBL Sarah Leigh Gene: cbl has been classified as Green List (High Evidence).
Primary lymphoedema v1.49 CBL Sarah Leigh Publications for gene: CBL were set to
Primary lymphoedema v1.48 CBL Sarah Leigh Classified gene: CBL as Red List (low evidence)
Primary lymphoedema v1.48 CBL Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.48 CBL Sarah Leigh Gene: cbl has been classified as Red List (Low Evidence).
Primary lymphoedema v1.47 BRAF Sarah Leigh Classified gene: BRAF as Green List (high evidence)
Primary lymphoedema v1.47 BRAF Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Sahar Mansour (St George's Hospital, London).
Primary lymphoedema v1.47 BRAF Sarah Leigh Gene: braf has been classified as Green List (High Evidence).
Primary lymphoedema v1.46 BRAF Sarah Leigh Publications for gene: BRAF were set to
Primary lymphoedema v1.45 SPRED1 Sahar Mansour reviewed gene: SPRED1: Rating: GREEN; Mode of pathogenicity: ; Publications: 17704776, 19366998, 19443465, 21649642, 21548021; Phenotypes: Legius syndrome 611431; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 SOS2 Sahar Mansour reviewed gene: SOS2: Rating: GREEN; Mode of pathogenicity: ; Publications: 25795793, 26173643; Phenotypes: Noonan syndrome 9 616559; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 SOS1 Sahar Mansour reviewed gene: SOS1: Rating: GREEN; Mode of pathogenicity: ; Publications: 19438935, 17143285, 17143282, 17586837; Phenotypes: Noonan syndrome 4 610733; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 SHOC2 Sahar Mansour reviewed gene: SHOC2: Rating: GREEN; Mode of pathogenicity: ; Publications: 19684605, 22528146, 23918763; Phenotypes: Noonan-like syndrome with loose anagen hair 607721; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 RIT1 Sahar Mansour reviewed gene: RIT1: Rating: GREEN; Mode of pathogenicity: ; Publications: 23791108, 25124994, 24939608; Phenotypes: Noonan syndrome 8 615355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 RAF1 Sahar Mansour reviewed gene: RAF1: Rating: GREEN; Mode of pathogenicity: ; Publications: 17603483, 17603482; Phenotypes: LEOPARD syndrome 2 611554, Noonan syndrome 5 611553; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 PTPN11 Sahar Mansour reviewed gene: PTPN11: Rating: GREEN; Mode of pathogenicity: ; Publications: 17603483, 11704759, 12529711, 12634870, 15384080, 15240615, 16263833, 17497712, 18678287; Phenotypes: LEOPARD syndrome 1 151100, Noonan syndrome 1 163950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 PPP1CB Sahar Mansour reviewed gene: PPP1CB: Rating: GREEN; Mode of pathogenicity: ; Publications: 27264673, 28211982, 27681385; Phenotypes: Noonan syndrome-like disorder with loose anagen hair 2 617506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 NRAS Sahar Mansour reviewed gene: NRAS: Rating: GREEN; Mode of pathogenicity: ; Publications: 19966803, 19775298; Phenotypes: Noonan syndrome 6 613224; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 NF1 Sahar Mansour reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: ; Publications: 16380919, 19845691, 12707950; Phenotypes: Neurofibromatosis-Noonan syndrome 601321, Neurofibromatosis, type 1 162200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 MAP2K2 Sahar Mansour reviewed gene: MAP2K2: Rating: GREEN; Mode of pathogenicity: ; Publications: 21396583, 23379592; Phenotypes: Cardiofaciocutaneous syndrome 4 615280; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 MAP2K1 Sahar Mansour reviewed gene: MAP2K1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21396583, 23321623; Phenotypes: Cardiofaciocutaneous syndrome 3 615279; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 LZTR1 Sahar Mansour reviewed gene: LZTR1: Rating: GREEN; Mode of pathogenicity: ; Publications: 25795793, 29469822; Phenotypes: Noonan syndrome 10 616564 , Schwannomatosis-2, susceptibility to 615670; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary lymphoedema v1.45 KRAS Sahar Mansour reviewed gene: KRAS: Rating: GREEN; Mode of pathogenicity: ; Publications: 21396583; Phenotypes: Noonan syndrome 3 609942, Cardiofaciocutaneous syndrome 2 615278; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 HRAS Sahar Mansour reviewed gene: HRAS: Rating: GREEN; Mode of pathogenicity: ; Publications: 16170316, 16969868, 16443854, 21396583; Phenotypes: Costello syndrome 218040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 CBL Sahar Mansour reviewed gene: CBL: Rating: GREEN; Mode of pathogenicity: ; Publications: 20619386, 20543203, 19571318; Phenotypes: Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 613563 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.45 BRAF Sahar Mansour reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: ; Publications: 19206169, 21396583; Phenotypes: LEOPARD syndrome 3 613707, Cardiofaciocutaneous syndrome 115150, Noonan syndrome 7 613706; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary lymphoedema v1.44 SPRED1 Sarah Leigh gene: SPRED1 was added
gene: SPRED1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: SPRED1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SPRED1 were set to Legius syndrome 611431
Primary lymphoedema v1.44 SOS2 Sarah Leigh gene: SOS2 was added
gene: SOS2 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: SOS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SOS2 were set to Noonan syndrome 9 616559
Mode of pathogenicity for gene: SOS2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 SOS1 Sarah Leigh gene: SOS1 was added
gene: SOS1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: SOS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SOS1 were set to Noonan syndrome 4 610733
Mode of pathogenicity for gene: SOS1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 SHOC2 Sarah Leigh gene: SHOC2 was added
gene: SHOC2 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: SHOC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SHOC2 were set to Noonan-like syndrome with loose anagen hair 607721
Primary lymphoedema v1.44 RIT1 Sarah Leigh gene: RIT1 was added
gene: RIT1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: RIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RIT1 were set to Noonan syndrome 8 615355
Mode of pathogenicity for gene: RIT1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 RAF1 Sarah Leigh gene: RAF1 was added
gene: RAF1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: RAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RAF1 were set to Noonan syndrome 5 611553; LEOPARD syndrome 2 611554
Mode of pathogenicity for gene: RAF1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 PTPN11 Sarah Leigh gene: PTPN11 was added
gene: PTPN11 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PTPN11 were set to Noonan syndrome 1 163950; LEOPARD syndrome 1 151100
Mode of pathogenicity for gene: PTPN11 was set to Other - please provide details in the comments
Primary lymphoedema v1.44 PPP1CB Sarah Leigh gene: PPP1CB was added
gene: PPP1CB was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: PPP1CB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PPP1CB were set to Noonan syndrome-like disorder with loose anagen hair 2 617506
Primary lymphoedema v1.44 NRAS Sarah Leigh gene: NRAS was added
gene: NRAS was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: NRAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: NRAS were set to Noonan syndrome 6 613224
Mode of pathogenicity for gene: NRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 NF1 Sarah Leigh gene: NF1 was added
gene: NF1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: NF1 were set to Neurofibromatosis-Noonan syndrome 601321; Neurofibromatosis, type 1 162200
Primary lymphoedema v1.44 MAP2K2 Sarah Leigh gene: MAP2K2 was added
gene: MAP2K2 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: MAP2K2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MAP2K2 were set to Cardiofaciocutaneous syndrome 4 615280
Mode of pathogenicity for gene: MAP2K2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 MAP2K1 Sarah Leigh gene: MAP2K1 was added
gene: MAP2K1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: MAP2K1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MAP2K1 were set to Cardiofaciocutaneous syndrome 3 615279
Mode of pathogenicity for gene: MAP2K1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 LZTR1 Sarah Leigh gene: LZTR1 was added
gene: LZTR1 was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: LZTR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: LZTR1 were set to Schwannomatosis-2, susceptibility to 615670; Noonan syndrome 10 616564
Primary lymphoedema v1.44 KRAS Sarah Leigh gene: KRAS was added
gene: KRAS was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: KRAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: KRAS were set to Noonan syndrome 3 609942; Cardiofaciocutaneous syndrome 2 615278
Mode of pathogenicity for gene: KRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 HRAS Sarah Leigh gene: HRAS was added
gene: HRAS was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: HRAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: HRAS were set to Costello syndrome 218040
Mode of pathogenicity for gene: HRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 CBL Sarah Leigh gene: CBL was added
gene: CBL was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: CBL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CBL were set to Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 613563
Mode of pathogenicity for gene: CBL was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.44 BRAF Sarah Leigh gene: BRAF was added
gene: BRAF was added to Primary lymphoedema. Sources: Expert Review
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: BRAF were set to LEOPARD syndrome 3 613707; Noonan syndrome 7 613706; Cardiofaciocutaneous syndrome 115150
Mode of pathogenicity for gene: BRAF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Primary lymphoedema v1.42 PIEZO1 Sarah Leigh Phenotypes for gene: PIEZO1 were changed from Lymphedema, hereditary, III 616843; Generalised lymphatic dysplasia to Lymphedema, hereditary, III 616843; Generalised lymphatic dysplasia
Primary lymphoedema v1.41 KIF11 Sarah Leigh Phenotypes for gene: KIF11 were changed from Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation, 152950 to Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation, MCLMR 152950
Primary lymphoedema v1.40 GJA1 Sarah Leigh Phenotypes for gene: GJA1 were changed from Oculodentodigital dysplasia with primary lymphoedem 164200 to Oculodentodigital dysplasia 164200
Primary lymphoedema v1.39 GATA2 Sarah Leigh Added comment: Comment on phenotypes: Emberger syndrome (Primary Lymphedema with Myelodysplasia) 614038
Primary lymphoedema v1.39 GATA2 Sarah Leigh Phenotypes for gene: GATA2 were changed from Primary Lymphedema with Myelodysplasia (Emberger Syndrome) 614038 to Emberger Syndrome 614038; {Myelodysplastic syndrome, susceptibility to} 614286
Primary lymphoedema v1.38 FLT4 Sarah Leigh Added comment: Comment on phenotypes: Previously known as Milroy disease.
Primary lymphoedema v1.38 FLT4 Sarah Leigh Phenotypes for gene: FLT4 were changed from Lymphedema, hereditary, IA 153100 to Lymphedema, hereditary, IA 153100
Primary lymphoedema v1.37 EPHB4 Sarah Leigh Deleted their review
Primary lymphoedema v1.37 EPHB4 Sarah Leigh Publications for gene: EPHB4 were set to 27400125
Primary lymphoedema v1.36 EPHB4 Sarah Leigh Added comment: Comment on phenotypes: This can manifest with fetal hydrops or Atrial septal defect.
Primary lymphoedema v1.36 EPHB4 Sarah Leigh Phenotypes for gene: EPHB4 were changed from Autosomal Dominant Lymphatic Related Hydrops Fetalis to Lymphatic malformation 7 617300
Primary lymphoedema v1.35 DCHS1 Ellen McDonagh reviewed gene: DCHS1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 ADAMTS3 Ellen McDonagh reviewed gene: ADAMTS3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 VEGFC Ellen McDonagh reviewed gene: VEGFC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 SOX18 Ellen McDonagh reviewed gene: SOX18: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 PTPN14 Ellen McDonagh reviewed gene: PTPN14: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 PIEZO1 Ellen McDonagh reviewed gene: PIEZO1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 KIF11 Ellen McDonagh reviewed gene: KIF11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 GJC2 Ellen McDonagh reviewed gene: GJC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 GJA1 Ellen McDonagh reviewed gene: GJA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 GATA2 Ellen McDonagh reviewed gene: GATA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 FOXC2 Ellen McDonagh reviewed gene: FOXC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 FLT4 Ellen McDonagh reviewed gene: FLT4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 FAT4 Ellen McDonagh reviewed gene: FAT4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 EPHB4 Ellen McDonagh reviewed gene: EPHB4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.35 CCBE1 Ellen McDonagh reviewed gene: CCBE1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary lymphoedema v1.34 DCHS1 Ellen McDonagh Source London South GLH was added to DCHS1.
Primary lymphoedema v1.34 ADAMTS3 Ellen McDonagh Source London South GLH was added to ADAMTS3.
Primary lymphoedema v1.34 VEGFC Ellen McDonagh Source London South GLH was added to VEGFC.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Primary lymphoedema v1.34 SOX18 Ellen McDonagh Source London South GLH was added to SOX18.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Primary lymphoedema v1.34 PTPN14 Ellen McDonagh Source London South GLH was added to PTPN14.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Primary lymphoedema v1.34 PIEZO1 Ellen McDonagh Source London South GLH was added to PIEZO1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Primary lymphoedema v1.34 KIF11 Ellen McDonagh Source London South GLH was added to KIF11.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Primary lymphoedema v1.34 GJC2 Ellen McDonagh Source London South GLH was added to GJC2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Primary lymphoedema v1.34 GJA1 Ellen McDonagh Source London South GLH was added to GJA1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Primary lymphoedema v1.34 GATA2 Ellen McDonagh Source London South GLH was added to GATA2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Primary lymphoedema v1.34 FOXC2 Ellen McDonagh Source London South GLH was added to FOXC2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Primary lymphoedema v1.34 FLT4 Ellen McDonagh Source London South GLH was added to FLT4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Primary lymphoedema v1.34 FAT4 Ellen McDonagh Source London South GLH was added to FAT4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Primary lymphoedema v1.34 EPHB4 Ellen McDonagh Source London South GLH was added to EPHB4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Primary lymphoedema v1.34 CCBE1 Ellen McDonagh Source London South GLH was added to CCBE1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Primary lymphoedema v1.32 Ellen McDonagh Panel name changed from Lymphatic Disorders to Primary lymphoedema
List of related panels changed from Meiges disease;Meige disease;Milroy disease;Lymphoedema distichiasis;Lipoedema disease;Primary lymphoedema to Lymphatic Disorders; Meiges disease; Meige disease; Milroy disease; Lymphoedema distichiasis; Lipoedema disease
Primary lymphoedema v1.31 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Primary lymphoedema v1.30 DCHS1 Rebecca Foulger Tag watchlist tag was added to gene: DCHS1.
Primary lymphoedema v1.30 DCHS1 Rebecca Foulger Classified gene: DCHS1 as Amber List (moderate evidence)
Primary lymphoedema v1.30 DCHS1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber as agreed with Helen Brittain and Anna De Burca: Insufficient evidence for diagnostic grade but features on St. George's Primary Lymphedema Disorders gene panel. Note that Prof. Sahar Mansour (St. George's hospital) confirmed via email thread that they have not seen cases.
Primary lymphoedema v1.30 DCHS1 Rebecca Foulger Gene: dchs1 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v1.29 ADAMTS3 Rebecca Foulger Tag watchlist tag was added to gene: ADAMTS3.
Primary lymphoedema v1.29 ADAMTS3 Rebecca Foulger Classified gene: ADAMTS3 as Amber List (moderate evidence)
Primary lymphoedema v1.29 ADAMTS3 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber as agreed with Helen Brittain and Anna De Burca: Insufficient evidence for diagnostic grade but features on St. George's Primary Lymphedema Disorders gene panel. Note that Prof. Sahar Mansour (St. George's hospital) confirmed via email thread that they have not seen cases.
Primary lymphoedema v1.29 ADAMTS3 Rebecca Foulger Gene: adamts3 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v1.28 DCHS1 Anna de Burca Added comment: Comment on publications: 3 homozygous variants in 3 unrelated consanguineous families with Van Maldergem syndrome. Lymphoedema is not a feature of Van Maldergem syndrome but Hennekam lymphoedema can be caused by mutations in FAT4 (the receptor for DHCS1) and this paper also reports variants in FAT4 in Van Maldergem syndrome. PMID: 24913602 states that there is considerable overlap in phenotype between the two conditions.
Primary lymphoedema v1.28 DCHS1 Anna de Burca Publications for gene: DCHS1 were set to
Primary lymphoedema v1.27 PTPN14 Rebecca Foulger Classified gene: PTPN14 as Green List (high evidence)
Primary lymphoedema v1.27 PTPN14 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green following request from Athina Ververi (GOSH), and advice from Helen Brittain. Green expert review, two literature cases (2010/PMID:20826270 and 2017/Bordbar et al), plus mouse model (PMID:20826270). PTPN14 is on the St. George's hospital Primary Lymphedema Disorders 15 Gene Panel, and it is recorded in literature and from clinical review that variants in PTPN14 are a rare cause of lymphedema.
Primary lymphoedema v1.27 PTPN14 Rebecca Foulger Gene: ptpn14 has been classified as Green List (High Evidence).
Primary lymphoedema v1.26 PTPN14 Rebecca Foulger commented on gene: PTPN14: Au et al (2010, PMID:20826270) provide a mouse model of PTPN14 deficiency where 14% of mutant animals showed swelling of limb extremeties.
Primary lymphoedema v1.26 DCHS1 Rebecca Foulger gene: DCHS1 was added
gene: DCHS1 was added to Lymphatic Disorders. Sources: UKGTN
Mode of inheritance for gene: DCHS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCHS1 were set to Van Maldergem syndrome 1, 601390
Added comment: Added DCHS1 to panel as requested by Athina Ververi at GOSH, because DCHS1 is on the St. George's lymphoedema 15-gene panel (September 2017). DCHS1 is a ligand for FAT4 (Green gene on this panel), and current evidence appears to be biochemical rather than variant case studies so kept rating as Red.
Sources: UKGTN
Primary lymphoedema v1.25 PTPN14 Rebecca Foulger Source UKGTN was added to PTPN14.
Primary lymphoedema v1.24 PTPN14 Rebecca Foulger Tag watchlist tag was added to gene: PTPN14.
Primary lymphoedema v1.24 ADAMTS3 Rebecca Foulger Source UKGTN was added to ADAMTS3.
Primary lymphoedema v1.23 ADAMTS3 Rebecca Foulger Classified gene: ADAMTS3 as Red List (low evidence)
Primary lymphoedema v1.23 ADAMTS3 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Red as currently insufficient cases for diagnostic grade (1 family in Brouillard et al. 2017).
Primary lymphoedema v1.23 ADAMTS3 Rebecca Foulger Gene: adamts3 has been classified as Red List (Low Evidence).
Primary lymphoedema v1.22 ADAMTS3 Rebecca Foulger commented on gene: ADAMTS3: Added to panel as requested by Athina Ververi (GOSH) based on presence of ADAMTS3 on the St. George's Primary Lymphedema Disorders 15 Gene Panel.
Primary lymphoedema v1.22 ADAMTS3 Rebecca Foulger Publications for gene: ADAMTS3 were set to 28985353; 28687807
Primary lymphoedema v1.21 ADAMTS3 Rebecca Foulger commented on gene: ADAMTS3: Mouse model for role of ADAMTS3 in lymphatic development is reported in PMID:26446156 (2016), with knockout mice exhibiting a massive lymphedema.
Primary lymphoedema v1.21 ADAMTS3 Rebecca Foulger commented on gene: ADAMTS3: PMID:28687807 (Jha et al., 2017) test a R565Q missense substitution in ADAMTS3 which was originally identified as a rare heterozygous polymoprhism in a lymphedema patient and in 6 unaffected members of the studied family as well as in 236 alleles in ExAC.
Primary lymphoedema v1.21 ADAMTS3 Rebecca Foulger commented on gene: ADAMTS3
Primary lymphoedema v1.21 ADAMTS3 Rebecca Foulger gene: ADAMTS3 was added
gene: ADAMTS3 was added to Lymphatic Disorders. Sources: Other
Mode of inheritance for gene: ADAMTS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS3 were set to 28985353; 28687807
Phenotypes for gene: ADAMTS3 were set to Hennekam syndrome; Hennekam lymphangiectasia-lymphedema syndrome 3
Primary lymphoedema v1.20 PTPN14 Rebecca Foulger commented on gene: PTPN14: Bordbar et al (2017, https://www.sciencedirect.com/science/article/pii/S2214540017300543) report an Iranian family with a single child with bilateral choanal atresia and infantile-onset lymphedema. Screening of PTPN14 revealed a novel homozygous frameshift insertion in exon4 (p.(Leu135Tyrfs*5). This forms the second reported family with choanal atresia and lymphedema syndrome.
Primary lymphoedema v1.20 PTPN14 Rebecca Foulger Publications for gene PTPN14 were changed from 20826270 to 20826270; 24167460
Primary lymphoedema v1.19 PTPN14 Rebecca Foulger commented on gene: PTPN14
Primary lymphoedema ZNHIT3 Rebecca Foulger commented on ZNHIT3
Primary lymphoedema ZNHIT3 Rebecca Foulger classified ZNHIT3 as red
Primary lymphoedema ZNHIT3 Rebecca Foulger added ZNHIT3 to panel
Primary lymphoedema ZNHIT3 Rebecca Foulger reviewed ZNHIT3
Primary lymphoedema CCDC88A Rebecca Foulger classified CCDC88A as red
Primary lymphoedema CCDC88A Rebecca Foulger commented on CCDC88A
Primary lymphoedema Sarah Leigh promoted panel to version 1
Primary lymphoedema CDC42 Sarah Leigh marked CDC42 as ready
Primary lymphoedema CDC42 Sarah Leigh commented on CDC42
Primary lymphoedema VEGFC Sarah Leigh marked VEGFC as ready
Primary lymphoedema VEGFC Sarah Leigh commented on VEGFC
Primary lymphoedema SOX18 Sarah Leigh marked SOX18 as ready
Primary lymphoedema PIEZO1 Sarah Leigh marked PIEZO1 as ready
Primary lymphoedema PIEZO1 Sarah Leigh commented on PIEZO1
Primary lymphoedema KIF11 Sarah Leigh marked KIF11 as ready
Primary lymphoedema KIF11 Sarah Leigh commented on KIF11
Primary lymphoedema IKBKG Sarah Leigh marked IKBKG as ready
Primary lymphoedema IKBKG Sarah Leigh commented on IKBKG
Primary lymphoedema GJC2 Sarah Leigh marked GJC2 as ready
Primary lymphoedema GJC2 Sarah Leigh commented on GJC2
Primary lymphoedema GATA2 Sarah Leigh marked GATA2 as ready
Primary lymphoedema GATA2 Sarah Leigh commented on GATA2
Primary lymphoedema GJA1 Sarah Leigh commented on GJA1
Primary lymphoedema CCDC88A Sarah Leigh marked CCDC88A as ready
Primary lymphoedema CCDC88A Sarah Leigh commented on CCDC88A
Primary lymphoedema AQP1 Sarah Leigh marked AQP1 as ready
Primary lymphoedema AQP1 Sarah Leigh commented on AQP1
Primary lymphoedema ALX3 Sarah Leigh marked ALX3 as ready
Primary lymphoedema ALX3 Sarah Leigh commented on ALX3
Primary lymphoedema ALX3 Sarah Leigh classified ALX3 as red
Primary lymphoedema PTPN14 Sarah Leigh marked PTPN14 as ready
Primary lymphoedema PTPN14 Sarah Leigh commented on PTPN14
Primary lymphoedema TTR Sarah Leigh marked TTR as ready
Primary lymphoedema TTR Sarah Leigh commented on TTR
Primary lymphoedema TTR Sarah Leigh classified TTR as red
Primary lymphoedema PTPN14 Pia Ostergaard commented on PTPN14
Primary lymphoedema TTR Pia Ostergaard reviewed TTR
Primary lymphoedema EPHB4 Pia Ostergaard reviewed EPHB4
Primary lymphoedema CDC42 Pia Ostergaard reviewed CDC42
Primary lymphoedema CCDC88A Pia Ostergaard reviewed CCDC88A
Primary lymphoedema AQP1 Pia Ostergaard reviewed AQP1
Primary lymphoedema ALX3 Pia Ostergaard reviewed ALX3
Primary lymphoedema PTPN14 Pia Ostergaard edited their review of PTPN14
Primary lymphoedema TTR Pia Ostergaard reviewed TTR
Primary lymphoedema EPHB4 Pia Ostergaard edited their review of EPHB4
Primary lymphoedema CDC42 Pia Ostergaard reviewed CDC42
Primary lymphoedema CCDC88A Pia Ostergaard reviewed CCDC88A
Primary lymphoedema AQP1 Pia Ostergaard reviewed AQP1
Primary lymphoedema ALX3 Pia Ostergaard reviewed ALX3
Primary lymphoedema EPHB4 Sarah Leigh marked EPHB4 as ready
Primary lymphoedema EPHB4 Sarah Leigh classified EPHB4 as green
Primary lymphoedema EPHB4 Sarah Leigh commented on EPHB4
Primary lymphoedema Ellen McDonagh approved panel