ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.1024C>T (p.Arg342Ter) (rs104894843)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723730 SCV000110101 pathogenic not provided 2018-06-28 criteria provided, single submitter clinical testing
Invitae RCV000011491 SCV000283689 pathogenic Fabry disease 2019-12-31 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the GLA gene (p.Arg342*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 88 amino acids of the GLA protein. This variant has been reported in individuals affected with Fabry disease (PMID: 8395937, 16595074, 19287194, 20505683, 23980562, 26297554, 20505683). Experimental studies have shown that this nonsense change abolishes GLA activity (PMID: 20505683). For these reasons, this variant has been classified as Pathogenic.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000011491 SCV000993561 pathogenic Fabry disease 2018-12-10 criteria provided, single submitter research
Integrated Genetics/Laboratory Corporation of America RCV000011491 SCV001363732 pathogenic Fabry disease 2019-05-13 criteria provided, single submitter clinical testing Variant summary: GLA c.1024C>T (p.Arg342X) 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. The variant was absent in 182951 control chromosomes (gnomAD). c.1024C>T has been reported in the literature in individuals affected with Fabry Disease (Davies_1993, Lee_2010, Uribe_2015, Rigoldi_2014). These data indicate that the variant is likely to be associated with disease. Patients carrying the variant of interest were found to have 0% GLA activity (Lee_2010, Uribe_2015). Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000011491 SCV000031723 pathogenic Fabry disease 1993-07-01 no assertion criteria provided literature only

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