ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.904G>T (p.Glu302Ter) (rs1060501136)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476810 SCV000545044 pathogenic Brugada syndrome 2019-06-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu302*) in the SCN5A gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN5A-related disease. ClinVar contains an entry for this variant (Variation ID: 406427). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in SCN5A are known to be pathogenic (PMID: 20129283, 22789973). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000657857 SCV000779615 pathogenic not provided 2018-05-25 criteria provided, single submitter clinical testing The E302X variant in the SCN5A gene has not been reported as a pathogenic or benign to our knowledge. However, this variant has been reported as pathogenic in ClinVar by another laboratory (SCV000545044.2; Landrum et al., 2016), and has been reported in one other individual who underwent genetic testing for arrhythmia at GeneDx. E302X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the SCN5A gene have been reported in Human Gene Mutation Database in association with Brugada syndrome and other SCN5A-related disorders (Stenson et al., 2014). Furthermore, the E302X variant is not observed in large population cohorts (Lek et al., 2016).

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