ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.85dup (p.Ala29fs)

dbSNP: rs1569306181
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Total submissions: 2
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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 RCV000780299 SCV000917461 pathogenic Fabry disease 2018-12-18 criteria provided, single submitter clinical testing Variant summary: GLA c.85dupG (p.Ala29GlyfsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. p.Glu103X, p.Trp162X, p.Arg220X). The variant was absent in 178735 control chromosomes (gnomAD). c.85dupG has been reported in the literature in individuals affected with Fabry Disease (Ashley_2001, Shin_2008). These data indicate that the variant may be associated with disease. In cells from a patient with this variant, enzyme activity was <10%, and did not increase in response to the pharmacological chaperone 1-deoxygalactonojirimycin (DGJ) (Shin_2008). 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 RCV000780299 SCV002183445 pathogenic Fabry disease 2021-03-07 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with Fabry disease (PMID: 11322659). ClinVar contains an entry for this variant (Variation ID: 632839). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ala29Glyfs*2) in the GLA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GLA are known to be pathogenic (PMID: 10666480, 12175777).

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