ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.254G>A (p.Gly85Asp)

dbSNP: rs1569304898
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000730015 SCV000857722 likely pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001855746 SCV002233961 pathogenic Fabry disease 2021-02-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly85 amino acid residue in GLA. Other variant(s) that disrupt this residue have been observed in individuals with GLA-related conditions (PMID: 20022777), which suggests that this may be a clinically significant amino acid residue. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with Fabry disease (PMID: 7599642, 27834756, 31392112). ClinVar contains an entry for this variant (Variation ID: 594665). This variant is also known as G85N. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 85 of the GLA protein (p.Gly85Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid.
Ambry Genetics RCV002424744 SCV002740646 likely pathogenic Cardiovascular phenotype 2019-12-03 criteria provided, single submitter clinical testing The p.G85D variant (also known as c.254G>A), located in coding exon 2 of the GLA gene, results from a G to A substitution at nucleotide position 254. The glycine at codon 85 is replaced by aspartic acid, an amino acid with similar properties. This variant has been reported in multiple males and females with symptoms of Fabry disease (Borgwardt L et al. Clin. Genet., 2013 May;83:432-8; Fledelius HC et al. ActaOphthalmol, 2015 May;93:258-64; Korsholm K et al. PLoS ONE, 2015 Dec;10:e0143940; Weidemann F et al. Mol. Genet. Metab., 201902;126:169-182; Frabasil J et al. JIMD Rep, 2019 Jul;48:45-52). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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