ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.830G>A (p.Trp277Ter)

dbSNP: rs886044766
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000723404 SCV000330964 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000286285 SCV000695749 pathogenic Fabry disease 2019-06-19 criteria provided, single submitter clinical testing Variant summary: GLA c.830G>A (p.Trp277X) 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. The variant was absent in 183402 control chromosomes (gnomAD). c.830G>A has been reported in the literature in multiple individuals affected with Classic Fabry Disease (Topaloglu_1999, Nakano_2015, Sivley_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000286285 SCV001587057 pathogenic Fabry disease 2023-07-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 280973). This premature translational stop signal has been observed in individual(s) with Fabry disease (PMID: 10666480). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp277*) 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).
Genome-Nilou Lab RCV000286285 SCV002054398 pathogenic Fabry disease 2021-07-15 criteria provided, single submitter clinical testing

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