ClinVar Miner

Submissions for variant NM_000335.4(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).
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."
Invitae RCV000471498 SCV000545066 pathogenic Brugada syndrome 2017-11-13 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.

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