Bleeding and platelet disorders
Gene: FLNAThe rating of this gene has been updated following NHS Genomic Medicine Service approval. It has been agreed that there is enough evidence to promote FLNA to green.Created: 4 Mar 2022, 9:41 a.m. | Last Modified: 4 Mar 2022, 9:41 a.m.
Panel Version: 1.33
Comment on mode of inheritance: Changed MOI from 'X-LINKED... biallelic mutations in females' to 'X-LINKED... monoallelic mutations in females may cause disease'.
FLNA-related periventricular nodular heterotopia (MIM# 300049) can be associated with macrothrombocytopenia and a bleeding tendency in some cases (PMID: 16684786; 21960593; 29449050; 32299270). Affected females with heterozygous variants in FLNA have been identified indicating XLD inheritance.
The association with macrothrombocytopenia has been supported by in vitro assays and animal model (PMID: 21652675; 21960593; 30602618; 31471375)Created: 12 Jul 2021, 2:13 p.m. | Last Modified: 12 Jul 2021, 2:13 p.m.
Panel Version: 1.29
Comment on list classification: Gene associated with multiple phenotypes which do not include haematological abnormalities. However, thrombocytopenia with or without platelet dysfunction has been reported in at least 11 individuals from 10 pedigrees with a total of 10 different FLNA variants. As this reaches threshold for inclusion as diagnostic-grade, this gene will be flagged for review at the next GMS panel update (added for-review tag)Created: 14 Jan 2021, 11:21 a.m. | Last Modified: 14 Jan 2021, 11:21 a.m.
Panel Version: 1.18
Note this recent review.Created: 12 Aug 2020, 4:18 a.m. | Last Modified: 12 Aug 2020, 4:18 a.m.
Panel Version: 1.6
Publications
Gene rating submitted by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test groupCreated: 18 Feb 2019, 11:23 a.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Macrothrombocytopenia
Gene rating submitted by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group.Created: 13 Feb 2019, 11:32 a.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Macrothrombocytopenia
Gene rating submitted by Mike Mitchell Viapath St. Thomas' Hospital January 2019 on behalf of London South GLH for the GMS Haematology specialist test group.Created: 7 Feb 2019, 1:21 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Macrothrombocytopenia (NO OMIM NUMBER)
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: As discussed in the GMS Haematology Specialist Test Group webex call 8th March 2019: The Specialist Test Group agreed that this gene should be rated Amber, so was downgraded from Green to Amber.Created: 18 Mar 2019, 3:28 p.m.
Initial gene list (Consensus Genes for SPEC HAEM Panels 31.01.19 North West v1 FINAL.xlsx) collated by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group. Gene Symbol submitted: FLNA; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Phenotypes: Macrothrombocytopenia (NO OMIM NUMBER); PMID(s): none submittedCreated: 18 Feb 2019, 11:28 a.m.
Initial gene list (Consensus Genes for Panels_Haem_SHEFFIELD-29.01.2019.xlsx) collated by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group. Gene Symbol submitted: FLNA; Suggested intial gene rating: I don't know; Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Phenotypes: N/A Macrothrombocytopenia; PMID(s): none submittedCreated: 13 Feb 2019, 11:34 a.m.
Initial gene list (Consensus Genes for Panels_Bleeding and Thrombosis_South London.xlsx) collated by Mike Mitchell Viapath St. Thomas' Hospital January 2019 on behalf of London South GLH for the GMS Haematology specialist test group. Gene Symbol submitted: FLNA; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Phenotypes: Macrothrombocytopenia (NO OMIM NUMBER); PMID(s): none submittedCreated: 7 Feb 2019, 1:28 p.m.
Initial gene list (Consensus Genes for Panels 17.12.18_Haem_WWMGLH_v3.xlxs) collated by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group. Gene Symbol submitted: FLNA; Suggested intial gene rating: Green List (high evidence); Are variants in this gene as part of your current diagnostic practice? Yes; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Phenotypes: Macrothrombocytopenia; (NO OMIM NUMBER); PMID(s): 21960593; 29449050Created: 5 Feb 2019, 1:26 p.m.
Gene rating submitted by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group.Created: 5 Feb 2019, 11:19 a.m.
Variants in this GENE are reported as part of current diagnostic practice
Tag for-review was removed from gene: FLNA.
Source Expert Review Green was added to FLNA. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Publications for gene: FLNA were set to 29449050; 21960593; 32299270
Mode of inheritance for gene: FLNA was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: FLNA were changed from (NO OMIM NUMBER); Macrothrombocytopenia to Heterotopia, periventricular, 1, OMIM:300049; Macrothrombocytopenia
Publications for gene: FLNA were set to 29449050; 21960593
Tag for-review tag was added to gene: FLNA.
Gene: flna has been classified as Amber List (Moderate Evidence).
Gene: flna has been classified as Amber List (Moderate Evidence).
Added phenotypes Macrothrombocytopenia for gene: FLNA
Source North West GLH was added to FLNA.
Added phenotypes Macrothrombocytopenia for gene: FLNA
Source Yorkshire and North East GLH was added to FLNA.
Added phenotypes Macrothrombocytopenia for gene: FLNA
Source London South GLH was added to FLNA.
Source NHS GMS was added to FLNA.
Source Expert Review Green was added to FLNA. Mode of inheritance for gene FLNA was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females Added phenotypes (NO OMIM NUMBER); Macrothrombocytopenia for gene: FLNA Publications for gene FLNA were changed from to 29449050; 21960593 Rating Changed from Red List (low evidence) to Green List (high evidence)
gene: FLNA was added gene: FLNA was added to Bleeding and platelet disorders. Sources: Wessex and West Midlands GLH Mode of inheritance for gene: FLNA was set to