ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.1196G>C (p.Trp399Ser) (rs782449839)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000209559 SCV000622181 uncertain significance Fabry disease 2017-05-03 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with serine at codon 399 of the GLA protein (p.Trp399Ser). The tryptophan residue is moderately conserved and there is a large physicochemical difference between tryptophan and serine. This variant is present in population databases (rs782449839, ExAC 0.1%). This variant has been reported in individuals affected with late-onset Fabry disease (PMID: 26415523, 28253518). ClinVar contains an entry for this variant (Variation ID: 217414). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Gharavi Laboratory,Columbia University RCV000782201 SCV000920678 uncertain significance not provided 2018-09-16 criteria provided, single submitter research
Albrecht-Kossel-Institute,Medical University Rostock RCV000209559 SCV000246105 likely pathogenic Fabry disease 2014-01-01 no assertion criteria provided research
Albrecht-Kossel-Institute,Medical University Rostock RCV000208881 SCV000246106 drug response Deoxygalactonojirimycin response 2014-01-01 no assertion criteria provided research
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000782201 SCV000925091 uncertain significance not provided 2017-11-01 no assertion criteria provided provider interpretation p.Trp399Ser (c.1196G>C) in GLA, Exon 7, (NM_000169.2; chrX-100652891-C-G) SCICD Classification: variant of uncertain significance, probably benign based on the allele frequency. We do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). Case data (not including our patient): Reported with Fabry. Per the lab report "This variant has been reported in individuals affected with late-onset Fabry disease (PMID: 26415523,)." Population data: Highest MAF in South Asian population: 0.07835% in gnomAD exomes (ExAC)

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