ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.404C>T (p.Ala135Val)

dbSNP: rs1569304221
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780295 SCV000917450 pathogenic Fabry disease 2018-08-14 criteria provided, single submitter clinical testing Variant summary: GLA c.404C>T (p.Ala135Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 178758 control chromosomes. c.404C>T has been reported in the literature in individuals affected with classic Fabry Disease (Dobrovolny_2005, Hulkova_2010, Uceyler_2011). These data indicate that the variant is likely to be associated with disease. In addition, a functional study has shown the variant to result in <10% of wild-type in vitro enzyme activity (Lukas_2013). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000780295 SCV001583999 pathogenic Fabry disease 2020-10-21 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 135 of the GLA protein (p.Ala135Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects GLA protein function (PMID: 23935525). This variant has been observed in individual(s) with Fabry disease (PMID: 23935525, 20628902, 15806320). ClinVar contains an entry for this variant (Variation ID: 632837).
Genome-Nilou Lab RCV000780295 SCV002054438 pathogenic Fabry disease 2021-07-15 criteria provided, single submitter clinical testing

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