Activity

Filter

Cancel
Date Panel Item Activity
108 actions
RASopathies v1.81 RRAS Sarah Leigh Classified gene: RRAS as Green List (high evidence)
RASopathies v1.81 RRAS Sarah Leigh Gene: rras has been classified as Green List (High Evidence).
RASopathies v1.80 RRAS Sarah Leigh Tag Q2_24_promote_green was removed from gene: RRAS.
RASopathies v1.80 RRAS Sarah Leigh Tag Q2_24_promote_green tag was added to gene: RRAS.
RASopathies v1.80 RRAS Sarah Leigh Publications for gene: RRAS were set to 24705357
RASopathies v1.79 RRAS Sarah Leigh edited their review of gene: RRAS: Added comment: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.; Changed rating: GREEN; Changed publications to: 24705357, 32815881, 34935735
RASopathies v1.79 RRAS Sarah Leigh Added comment: Comment on phenotypes: Phenotype from Gen2Phen
RASopathies v1.79 RRAS Sarah Leigh Phenotypes for gene: RRAS were changed from Noonan syndrome to RRAS-related atypical Noonan syndrome
RASopathies v1.78 MAP4K4 Irina Ziravecka gene: MAP4K4 was added
gene: MAP4K4 was added to RASopathies. Sources: Literature
Mode of inheritance for gene: MAP4K4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP4K4 were set to PMID: 37126546
Phenotypes for gene: MAP4K4 were set to neurodevelopmental differences; multiple congenital anomalies
Mode of pathogenicity for gene: MAP4K4 was set to Other
Review for gene: MAP4K4 was set to GREEN
Added comment: PMID: 37126546 - "a cohort of 26 affected individuals from 21 unrelated families with neurodevelopmental differences, cardiac issues, and CFAs who share a phenotype overlap with RASopathies and harbor a series of rare variants in MAP4K4.
Functional studies in zebrafish showed that MAP4K4 variants caused hypomorphic, LOF, or DN effects."
Sources: Literature
RASopathies v1.78 ISCA-37431-Loss Arina Puzriakova commented on Region: ISCA-37431-Loss
RASopathies v1.78 ISCA-37431-Loss Arina Puzriakova GRCh38 position for ISCA-37431-Loss was changed from 30835804-31891648 to 30780079-31937008.
Required Overlap Percentage for ISCA-37431-Loss was changed from 80 to 60.
RASopathies v1.77 SPRED2 Ivone Leong Classified gene: SPRED2 as Green List (high evidence)
RASopathies v1.77 SPRED2 Ivone Leong Added comment: Comment on list classification: There is enough evidence for this gene to be Green.
RASopathies v1.77 SPRED2 Ivone Leong Gene: spred2 has been classified as Green List (High Evidence).
RASopathies v1.76 SPRED2 Ivone Leong Tag Q1_22_rating was removed from gene: SPRED2.
RASopathies v1.76 SPRED2 Ivone Leong Entity copied from Intellectual disability v3.1496
RASopathies v1.76 SPRED2 Ivone Leong gene: SPRED2 was added
gene: SPRED2 was added to RASopathies. Sources: Literature,Expert Review Amber
Q1_22_rating tags were added to gene: SPRED2.
Mode of inheritance for gene: SPRED2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPRED2 were set to 34626534
Phenotypes for gene: SPRED2 were set to developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt
RASopathies v1.75 MRAS Arina Puzriakova Phenotypes for gene: MRAS were changed from Noonan syndrome 11, 618499 to Noonan syndrome 11, OMIM:618499; Noonan syndrome 11, MONDO:0032786
RASopathies v1.74 HRAS Arina Puzriakova Publications for gene: HRAS were set to 16170316; 16969868; 16443854; 21396583
RASopathies v1.73 HRAS Mehdi Montazer reviewed gene: HRAS: Rating: GREEN; Mode of pathogenicity: Other; Publications: https://doi.org/10.1038/s41431-020-0662-4; Phenotypes: hypertrophic cardiomyopathy, Chiari 1 malformation, ectodermal findings; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
RASopathies v1.73 SHOC2 Ivone Leong Phenotypes for gene: SHOC2 were changed from Noonan-like syndrome with loose anagen hair to Noonan syndrome-like with loose anagen hair 1, 607721
RASopathies v1.72 RRAS2 Ivone Leong Publications for gene: RRAS2 were set to 31130282
RASopathies v1.71 RRAS2 Ivone Leong Phenotypes for gene: RRAS2 were changed from Noonan syndrome 12, OMIM #618624 to Noonan syndrome 12, 618624
RASopathies v1.70 NRAS Ivone Leong Phenotypes for gene: NRAS were changed from Noonan syndrome 6 613224; Cardio-Facio-cutanenous syndrome; CFC Syndrome to Noonan syndrome 6 613224; Cardio-Facio-cutanenous syndrome
RASopathies v1.69 MRAS Ivone Leong Publications for gene: MRAS were set to 28289718
RASopathies v1.68 MRAS Ivone Leong Phenotypes for gene: MRAS were changed from Noonan syndrome to Noonan syndrome 11, 618499
RASopathies v1.67 MAP2K1 Ivone Leong Phenotypes for gene: MAP2K1 were changed from Cardiofaciocutaneous syndrome 3; Cardiofaciocutaneous Syndrome; Cardio-Facio-Cutaneous syndrome; CFC syndrome; LEOPARD syndrome; ?Noonan syndrome to Cardiofaciocutaneous syndrome 3, 615279; LEOPARD syndrome; ?Noonan syndrome
RASopathies v1.66 MAP2K1 Ivone Leong Added comment: Comment on publications: PMID: 23321623 (publication referring to Noonan syndrome association).
RASopathies v1.66 MAP2K1 Ivone Leong Publications for gene: MAP2K1 were set to 21396583; 23321623 (publication referring to Noonan syndrome association).
RASopathies v1.65 MAP2K1 Ivone Leong Publications for gene: MAP2K1 were set to PMID: 21396583; 23321623 (publication referring to Noonan syndrome association).
RASopathies v1.64 LZTR1 Ivone Leong Phenotypes for gene: LZTR1 were changed from Noonan syndrome 10 616564; Schwannomatosis-2, susceptibility to 615670 to Noonan syndrome 10 616564; Schwannomatosis-2, susceptibility to 615670; Noonan syndrome 2, 605275
RASopathies v1.63 HRAS Ivone Leong Phenotypes for gene: HRAS were changed from Costello syndrome to Costello syndrome, 218040
RASopathies v1.62 RREB1 Arina Puzriakova Classified gene: RREB1 as Red List (low evidence)
RASopathies v1.62 RREB1 Arina Puzriakova Added comment: Comment on list classification: Rating Red as currently only a single individuals reported (PMID:32938917) with clinical features consistent with a Noonan-spectrum disorder and a 6p-interstitial microdeletion which encompassed 11 genes, including RREB1. Additional cases would help delineate the relevance of the RREB1 gene to the observed phenotype.
RASopathies v1.62 RREB1 Arina Puzriakova Gene: rreb1 has been classified as Red List (Low Evidence).
RASopathies v1.61 RREB1 Zornitza Stark gene: RREB1 was added
gene: RREB1 was added to RASopathies. Sources: Literature
Mode of inheritance for gene: RREB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RREB1 were set to 32938917
Phenotypes for gene: RREB1 were set to Noonan syndrome-like disorder
Review for gene: RREB1 was set to RED
Added comment: Single individual reported with Noonan syndrome-like features and a deletion encompassing RREB1. Overlapping deletions in publicly reported databases examined, and RREB1 postulated to be the key gene. Rreb1 hemizygous mice display orbital hypertelorism and age dependent cardiac hypertrophy. RREB1 recruits SIN3A and KDM1A to an RRE in target promoters in human and murine cells to control histone H3K4 methylation of MAPK pathway genes. In summary, single well phenotyped individual with a CNV and experimental data to support gene-disease association.
Sources: Literature
RASopathies v1.61 RRAS Arina Puzriakova Classified gene: RRAS as Amber List (moderate evidence)
RASopathies v1.61 RRAS Arina Puzriakova Added comment: Comment on list classification: Rated Amber as additional cases required to validate the causal association with the phenotype.

Currently not associated with any phenotype in OMIM but a probable gene for Atypical Noonan Syndrome in G2P.
RASopathies v1.61 RRAS Arina Puzriakova Gene: rras has been classified as Amber List (Moderate Evidence).
RASopathies v1.60 RRAS2 Arina Puzriakova Added comment: Comment on mode of pathogenicity: All variants reported increase activation of the MAPK cascade.
RASopathies v1.60 RRAS2 Arina Puzriakova Mode of pathogenicity for gene: RRAS2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
RASopathies v1.59 RRAS2 Arina Puzriakova Classified gene: RRAS2 as Green List (high evidence)
RASopathies v1.59 RRAS2 Arina Puzriakova Added comment: Comment on list classification: At least nine unrelated pedigrees with Noonan syndrome, associated with monoallelic variants in this gene.
RASopathies v1.59 RRAS2 Arina Puzriakova Gene: rras2 has been classified as Green List (High Evidence).
RASopathies v1.58 RRAS2 Arina Puzriakova reviewed gene: RRAS2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 31130282, 31130285; Phenotypes: Noonan syndrome 12, 618624; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
RASopathies v1.58 RASA2 Arina Puzriakova Publications for gene: RASA2 were set to PMID: 25049390
RASopathies v1.57 RASA2 Arina Puzriakova Classified gene: RASA2 as Amber List (moderate evidence)
RASopathies v1.57 RASA2 Arina Puzriakova Added comment: Comment on list classification: Three unrelated cases but very limited details and no segregation data. Not associated with any phenotype in OMIM or G2P. Rated Amber, awaiting additional publications/clinical evidence to corroborate causality.
RASopathies v1.57 RASA2 Arina Puzriakova Gene: rasa2 has been classified as Amber List (Moderate Evidence).
RASopathies v1.56 MRAS Arina Puzriakova Classified gene: MRAS as Green List (high evidence)
RASopathies v1.56 MRAS Arina Puzriakova Gene: mras has been classified as Green List (High Evidence).
RASopathies v1.55 MRAS Arina Puzriakova changed review comment from: PMID: 28289718 (2017) - In two unrelated patients with Noonan syndrome and cardiac hypertrophy, trio WES/targeted sequencing revealed de novo missense variants (c.68G>T, p.G23V and c.203C>T, p.T68I) in the MRAS gene. Functional studies of the p.Gly23Val variant showed the change yields a constitutively active form of MRAS.

PMID: 31173466 (2019) - One patient with a severe a Noonan syndrome phenotype, associated with a de novo MRAS variant (c.212A>G, p.Q71R). Functional studies were not performed.

PMID: 31108500 (2020) - Two unrelated patients with Noonan syndrome, including hypertrophic cardiomyopathy and dysmorphic features. Targeted sequencing revealed de novo activating MRAS variants (c.203C>T, p.T68I and c.67G>C, p.G23R). Functional studies demonstrated that the variants yields a constitutively active form of MRAS.; to: Associated with Noonan syndrome in OMIM and G2P (confirmed).

PMID: 28289718 (2017) - In two unrelated patients with Noonan syndrome and cardiac hypertrophy, trio WES/targeted sequencing revealed de novo missense variants (c.68G>T, p.G23V and c.203C>T, p.T68I) in the MRAS gene. Functional studies of the p.Gly23Val variant showed the change yields a constitutively active form of MRAS.

PMID: 31173466 (2019) - One patient with a severe a Noonan syndrome phenotype, associated with a de novo MRAS variant (c.212A>G, p.Q71R). Functional studies were not performed.

PMID: 31108500 (2020) - Two unrelated patients with Noonan syndrome, including hypertrophic cardiomyopathy and dysmorphic features. Targeted sequencing revealed de novo activating MRAS variants (c.203C>T, p.T68I and c.67G>C, p.G23R). Functional studies demonstrated that the variants yields a constitutively active form of MRAS.
RASopathies v1.55 MRAS Arina Puzriakova reviewed gene: MRAS: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 28289718, 31173466, 31108500; Phenotypes: Noonan syndrome 11, 618499; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
RASopathies v1.55 MRAS Zornitza Stark changed review comment from: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen.
Sources: Expert list; to: Two unrelated individuals reported with de novo variants in this gene initially. Rated as LIMITED by ClinGen in 2018. Note 4 further individuals reported since.
Sources: Expert list
RASopathies v1.55 MRAS Zornitza Stark edited their review of gene: MRAS: Changed rating: GREEN; Changed publications: 28289718, 31173466, 31108500, 31173466
RASopathies v1.55 MRAS Zornitza Stark gene: MRAS was added
gene: MRAS was added to RASopathies. Sources: Expert list
Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MRAS were set to 28289718
Phenotypes for gene: MRAS were set to Noonan syndrome
Review for gene: MRAS was set to AMBER
Added comment: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen.
Sources: Expert list
RASopathies v1.55 RASA2 Zornitza Stark reviewed gene: RASA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 25049390; Phenotypes: Noonan syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
RASopathies v1.55 A2ML1 Zornitza Stark reviewed gene: A2ML1: Rating: RED; Mode of pathogenicity: None; Publications: 24939586, 25862627; Phenotypes: Noonan syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
RASopathies v1.55 RRAS2 Zornitza Stark gene: RRAS2 was added
gene: RRAS2 was added to RASopathies. Sources: Expert list
Mode of inheritance for gene: RRAS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAS2 were set to 31130282
Phenotypes for gene: RRAS2 were set to Noonan syndrome 12, OMIM #618624
Review for gene: RRAS2 was set to GREEN
gene: RRAS2 was marked as current diagnostic
Added comment: Six unrelated families reported
Sources: Expert list
RASopathies v1.55 RRAS Zornitza Stark gene: RRAS was added
gene: RRAS was added to RASopathies. Sources: Expert list
Mode of inheritance for gene: RRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAS were set to 24705357
Phenotypes for gene: RRAS were set to Noonan syndrome
Review for gene: RRAS was set to AMBER
Added comment: Two individuals reported. One de novo variant, the inheritance of the other variant uncertain. Some supportive functional data. Rated as LIMITED by ClinGen.
Sources: Expert list
RASopathies v1.53 SPRED1 Sarah Leigh Phenotypes for gene: SPRED1 were changed from Legius Syndrome; Neurofibromatosis-like syndrome to Legius syndrome 611431
RASopathies v1.52 SPRED1 Sarah Leigh Publications for gene: SPRED1 were set to PMID: 17704776; 19366998; 19443465; 21649642; 21548021
RASopathies v1.51 SOS2 Sarah Leigh Phenotypes for gene: SOS2 were changed from Noonan syndrome 9 to Noonan syndrome 9 616559
RASopathies v1.50 SOS1 Sarah Leigh Phenotypes for gene: SOS1 were changed from Noonan syndrome; Noonan syndrome 4 to Noonan syndrome 4 610733
RASopathies v1.49 SOS1 Sarah Leigh Publications for gene: SOS1 were set to PMID: 19438935; 17143285; 17143282; 17586837
RASopathies v1.48 SHOC2 Sarah Leigh commented on gene: SHOC2
RASopathies v1.48 SHOC2 Sarah Leigh Publications for gene: SHOC2 were set to PMID: 19684605; 22528146; 23918763
RASopathies v1.47 RIT1 Sarah Leigh Publications for gene: RIT1 were set to PMID: 23791108; 25124994; 24939608
RASopathies v1.46 RIT1 Sarah Leigh Phenotypes for gene: RIT1 were changed from Noonan syndrome 8; Noonan syndrome type 8 to Noonan syndrome 8 615355
RASopathies v1.45 RAF1 Sarah Leigh Publications for gene: RAF1 were set to PMID: 17603483; 17603482
RASopathies v1.44 RAF1 Sarah Leigh Phenotypes for gene: RAF1 were changed from Noonan syndrome; Noonan syndrome 5; LEOPARD syndrome; LEOPARD syndrome 2 to LEOPARD syndrome 2 611554; Noonan syndrome 5 611553
RASopathies v1.43 PTPN11 Sarah Leigh Publications for gene: PTPN11 were set to PMID: 17603483; 11704759; 12529711; 12634870; 15384080; 15240615; 16263833; 17497712; 18678287
RASopathies v1.42 PTPN11 Sarah Leigh Phenotypes for gene: PTPN11 were changed from LEOPARD syndrome; LEOPARD syndrome 1; Noonan syndrome; Noonan syndrome 1 to LEOPARD syndrome 1 151100; Noonan syndrome 1 163950
RASopathies v1.41 NRAS Sarah Leigh Phenotypes for gene: NRAS were changed from Noonan syndrome; Noonan syndrome 6; Cardio-Facio-cutanenous syndrome; CFC Syndrome to Noonan syndrome 6 613224; Cardio-Facio-cutanenous syndrome; CFC Syndrome
RASopathies v1.40 NRAS Sarah Leigh Publications for gene: NRAS were set to PMID: 19966803; 19775298
RASopathies v1.39 NF1 Sarah Leigh Publications for gene: NF1 were set to PMID: 16380919; 19845691; 12707950
RASopathies v1.38 NF1 Sarah Leigh Phenotypes for gene: NF1 were changed from Neurofibromatosis-Noonan syndrome 601321 to Neurofibromatosis-Noonan syndrome 601321; Neurofibromatosis, type 1 162200
RASopathies v1.37 NF1 Sarah Leigh Phenotypes for gene: NF1 were changed from Neurofibromatosis-Noonan Syndrome; Neurofibromatosis Noonan syndrome; Noonan syndrome; Neurofibromatosis syndrome 1 to Neurofibromatosis-Noonan syndrome 601321
RASopathies v1.36 MAP2K2 Sarah Leigh Publications for gene: MAP2K2 were set to PMID: 21396583; 23379592
RASopathies v1.35 MAP2K2 Sarah Leigh Phenotypes for gene: MAP2K2 were changed from Cardiofaciocutaneous syndrome 4; Cardio-Facio-Cutaneous syndrome type 4; Cardiofaciocutaneous Syndrome; Cardio-Facio-Cutaneous syndrome; CFC syndrome to Cardiofaciocutaneous syndrome 4 615280
RASopathies v1.34 LZTR1 Sarah Leigh Phenotypes for gene: LZTR1 were changed from Noonan syndrome 10; Prenatal hydrops; increased nuchal translucency; cardiac findings to Noonan syndrome 10 616564; Schwannomatosis-2, susceptibility to 615670
RASopathies v1.33 KRAS Sarah Leigh Phenotypes for gene: KRAS were changed from Noonan syndrome 3; Noonan syndrome; Cardiofaciocutaneous syndrome 2; Cardiofaciocutaneous Syndrome; Cardio-Facio-Cutaneous syndrome; CFC syndrome to Noonan syndrome 3 609942; Cardiofaciocutaneous syndrome 2 615278
RASopathies v1.32 HRAS Sarah Leigh Publications for gene: HRAS were set to PMID: 16170316; 16969868; 16443854; 21396583
RASopathies v1.31 CBL Sarah Leigh Phenotypes for gene: CBL were changed from Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia to Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 613563
RASopathies v1.30 CBL Sarah Leigh Publications for gene: CBL were set to PMID: 20619386; 20543203; 19571318
RASopathies v1.29 BRAF Sarah Leigh Phenotypes for gene: BRAF were changed from LEOPARD Syndrome; Noonan Syndrome; Cardiofaciocutaneous Syndrome; LEOPARD syndrome 3; Cardio-facio-cutaneous syndrome to LEOPARD syndrome 3 613707; Cardiofaciocutaneous syndrome 115150; Noonan syndrome 7 613706
RASopathies v1.28 BRAF Sarah Leigh Publications for gene: BRAF were set to PMID: 19206169; 21396583; PMID: 19206169; 21396583; PMID: 19206169; 21396583; PMID: 19206169; 21396583
RASopathies v1.27 ISCA-37431-Loss Louise Daugherty Region: ISCA-37431-Loss was added
Region: ISCA-37431-Loss was added to RASopathies. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37431-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for Region: ISCA-37431-Loss were set to dysmorphic features, cardiac anomalies and mental retardation; 613675; variable facial dysmorphism, cafe-au-lait spots, neurofibromas and Lisch nodules in the iris, mental retardation, developmental delay, an excessive number of early-onset neurofibromas and an increased risk for malignant peripheral nerve sheath tumors; NEUROFIBROMATOSIS 1 MICRODELETION SYNDROME; NF1 MICRODELETION SYNDROME; Chromosome 17q11.2 deletion syndrome, 1.4Mb
RASopathies A2ML1 Ellen McDonagh commented on gene: A2ML1
RASopathies A2ML1 Ellen McDonagh commented on gene: A2ML1
RASopathies A2ML1 Ellen McDonagh commented on gene: A2ML1
RASopathies LZTR1 Andrea Haworth reviewed LZTR1
RASopathies PPP1CB Rebecca Foulger classified PPP1CB as green
RASopathies PPP1CB Rebecca Foulger commented on PPP1CB
RASopathies PPP1CB Rebecca Foulger commented on PPP1CB
RASopathies PPP1CB Rebecca Foulger commented on PPP1CB
RASopathies PPP1CB Rebecca Foulger added PPP1CB to panel
RASopathies PPP1CB Rebecca Foulger reviewed PPP1CB
RASopathies LZTR1 Alice Gardham marked LZTR1 as ready
RASopathies LZTR1 Alice Gardham classified LZTR1 as green
RASopathies LZTR1 Alice Gardham reviewed LZTR1
RASopathies SOS2 Alice Gardham marked SOS2 as ready
RASopathies SOS2 Alice Gardham classified SOS2 as green
RASopathies SOS2 Alice Gardham reviewed SOS2
RASopathies LZTR1 Ellen McDonagh added LZTR1 to panel
RASopathies LZTR1 Ellen McDonagh reviewed LZTR1
RASopathies SOS2 Ellen McDonagh added SOS2 to panel
RASopathies SOS2 Ellen McDonagh reviewed SOS2