Submissions for variant NM_000169.3(GLA):c.85G>T (p.Ala29Ser)

dbSNP: rs142449183

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001187973	SCV001354915	uncertain significance	Fabry disease	2023-03-15	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with serine at codon 29 of the GLA protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with GLA-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae	RCV001187973	SCV001414150	uncertain significance	Fabry disease	2021-09-03	criteria provided, single submitter	clinical testing	This sequence change replaces alanine with serine at codon 29 of the GLA protein (p.Ala29Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with Fabry disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 925806). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV001751339	SCV001987632	uncertain significance	not provided	2019-05-20	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Genome-Nilou Lab	RCV001187973	SCV002054362	uncertain significance	Fabry disease	2021-07-15	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001751339	SCV003816823	uncertain significance	not provided	2020-12-10	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001187973	SCV002081353	uncertain significance	Fabry disease	2020-08-12	no assertion criteria provided	clinical testing