ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.692A>C (p.Asp231Ala) (rs1569303295)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701032 SCV000829814 uncertain significance Fabry disease 2018-05-10 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with alanine at codon 231 of the GLA protein (p.Asp231Ala). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GLA-related disease. 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. Three different missense substitutions at this codon (p.Asp231Asn, p.Asp231Val, p.Asp231Gly) have been reported in individuals affected with Fabry disease (PMID: 8863162, 18205205, 19287194). 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.
Blueprint Genetics RCV000788378 SCV000927464 likely pathogenic not provided 2017-11-07 criteria provided, single submitter clinical testing

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