ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.734G>A (p.Trp245Ter)

dbSNP: rs398123220
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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) RCV000078295 SCV000110135 pathogenic not provided 2017-09-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193671 SCV001362667 pathogenic Fabry disease 2019-10-22 criteria provided, single submitter clinical testing Variant summary: GLA c.734G>A (p.Trp245X) 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 183472 control chromosomes. c.734G>A has been reported in the literature in individuals affected with Fabry Disease (Germain_2015, Germain_2002, Sakurab_2018, Tsukimura_2014). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab RCV001193671 SCV002054414 pathogenic Fabry disease 2021-07-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001193671 SCV002139142 pathogenic Fabry disease 2021-04-08 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: 12428061). ClinVar contains an entry for this variant (Variation ID: 92564). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp245*) 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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