ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.379A>T (p.Lys127Ter)

dbSNP: rs2147477845
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001381526 SCV001579965 pathogenic Fabry disease 2020-09-01 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in GLA are known to be pathogenic (PMID: 10666480, 12175777). This variant has been observed in an individual with Fabry disease (PMID: 16595074). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys127*) in the GLA gene. It is expected to result in an absent or disrupted protein product.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001381526 SCV001623261 pathogenic Fabry disease 2021-05-04 criteria provided, single submitter clinical testing Variant summary: GLA c.379A>T (p.Lys127X) 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 (Example: c.485G>A p.Trp162X; c.658C>T p.Arg220X). The variant was absent in 183372 control chromosomes (gnomAD). c.379A>T has been reported in the literature in an individual affected with classic phenotype of Fabry Disease (Shabbeer_2006). Enzyme activity from a patient (with a Classic phenotype of Fabry disease) derived sample carrying the variant of interest show reduced activity (Shabbeer_2006). 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.
Genome-Nilou Lab RCV001381526 SCV002054440 pathogenic Fabry disease 2021-07-15 criteria provided, single submitter clinical testing

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