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 2015-04-22 criteria provided, single submitter clinical testing p.Gln859Ter (CAG>TAG): c.2575 C>T in exon 16 of the SCN5A gene (NM_198056.2)The Q859X mutation in the SCN5A gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Q859X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense mutations in the SCN5A gene have been reported in association with SCN5A-related disorders. In summary, Q859X in the SCN5A gene is interpreted as a disease-causing mutation. The variant is found in BRUGADA,CARDIOMYOPATHY panel(s).
Invitae RCV000471498 SCV000545066 pathogenic Brugada syndrome 2019-12-17 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.
Integrated Genetics/Laboratory Corporation of America 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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