ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.886A>G (p.Met296Val)

dbSNP: rs104894830
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000179267 SCV000231489 pathogenic not provided 2015-11-23 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001185735 SCV001352002 likely pathogenic Fabry disease 2022-08-31 criteria provided, single submitter clinical testing This missense variant replaces methionine with valine at codon 296 of the GLA protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). An experimental study has shown that this variant leads to 11-12% residual GLA enzyme activity when expressed in COS-7 cells (PMID: 17555407). This variant has been reported in an adult male affected with mild cardiac variant of Fabry disease (PMID: 1846223). Residual GLA enzyme activity was detectable in cells from this patient. This variant has been reported in individuals affected with Fabry disease with symptoms confined to the kidney (PMID: 29204651, 30890379, 31798221; doi:10.1016/j.ymgme.2016.11.104; doi: 10.5812/numonthly.105759). A different missense variant occurring at the same codon, p.Met296Ile (Clinvar variation ID 10763), has been reported in multiple Japanese males affected with mild, late-onset Fabry disease (PMID: 7596372, 30386727), indicating that methionine at this position is important for GLA protein function. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.
Baylor Genetics RCV001185735 SCV001522948 pathogenic Fabry disease 2020-11-05 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Genome-Nilou Lab RCV001185735 SCV002054395 likely pathogenic Fabry disease 2021-07-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001185735 SCV002784805 likely pathogenic Fabry disease 2021-07-13 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000179267 SCV003826327 pathogenic not provided 2022-11-17 criteria provided, single submitter clinical testing
GeneDx RCV000179267 SCV005201464 pathogenic not provided 2023-11-13 criteria provided, single submitter clinical testing Published functional studies demonstrate reduced alpha-galactosidase activity (PMID: 17555407, 21598360); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21598360, 1846223, 24386359, 25382311, 17555407, 29204651, 26833297, 27535533, 20031620, 20108436, 28615118, 27560961)
OMIM RCV000011464 SCV000031696 pathogenic Fabry disease, cardiac variant 1991-02-07 no assertion criteria provided literature only

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