ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.2575C>T (p.Gln859Ter) (rs794728865)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183005 SCV000235411 pathogenic not provided 2019-12-19 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016)
Invitae RCV000471498 SCV000545066 pathogenic Brugada syndrome 2019-12-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 859 (p.Gln859*) of the SCN5A gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in SCN5A are known to be pathogenic (PMID: 20129283, 22789973). ClinVar contains an entry for this variant (Variation ID: 201475). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588650 SCV000700027 likely pathogenic Long QT syndrome 1 2017-01-23 criteria provided, single submitter clinical testing Variant summary: The SCN5A c.2575C>T (p.Gln859X) variant results in a premature termination codon, predicted to cause a truncated or absent SCN5A protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as likely pathogenic/pathogenic by our laboratory (e.g. c.3946C>T (p.Arg1316X). The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP), nor has it been, to our knowledge, reported in affected individuals via publications. A clinical diagnostic laboratory classifies the variant as "pathogenic." Therefore, until additional information becomes available, the variant of interest has been classified as "likely pathogenic."

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