ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.888G>T (p.Met296Ile)

dbSNP: rs104894846
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001919968 SCV002165842 pathogenic Fabry disease 2022-12-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Met296 amino acid residue in GLA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27560961; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects GLA function (PMID: 7596372). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GLA protein function. ClinVar contains an entry for this variant (Variation ID: 1396452). This missense change has been observed in individual(s) with Fabry disease (PMID: 7596372, 12911529). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 296 of the GLA protein (p.Met296Ile).
Fulgent Genetics, Fulgent Genetics RCV001919968 SCV002811540 pathogenic Fabry disease 2021-09-30 criteria provided, single submitter clinical testing

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