ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.125T>C (p.Met42Thr) (rs398123201)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723538 SCV000110106 pathogenic not provided 2018-03-06 criteria provided, single submitter clinical testing
Invitae RCV000078266 SCV000825681 pathogenic Fabry disease 2018-05-17 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 42 of the GLA protein (p.Met42Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with low alpha-galactosidase enzyme activity, findings that are highly specific for Fabry disease (Pubmed: 12175777, 15776423, Invitae). ClinVar contains an entry for this variant (Variation ID: 92541). Experimental studies have shown that this missense change results in a GLA protein with greatly reduced enzymatic activity (PMID: 26415523). The p.Met42 amino acid residue in GLA has been determined to be clinically significant (PMID: 23935525, 19287194, 18205205, 8875188). This suggests that variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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