ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.4147C>T (p.Gln1383Ter) (rs1553695282)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498546 SCV000589533 likely pathogenic not provided 2016-02-11 criteria provided, single submitter clinical testing The Q1383X variant in the SCN5A gene has been reported in a man diagnosed at age 40 with Brugada syndrome who also harbored a L619F variant in the SCN5A gene that was reported to be pathogenic (Kapplinger et al., 2010). Although it was not reported if these variants were in cis or trans, Kapplinger et al. (2010) found that both the Q1383X and L619F variants were absent in >2600 control alleles. Moreover, the Q1383X likely pathogenic variant 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 HGMD in association with Brugada syndrome (Stenson et al., 2014). Furthermore, the Q1383X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
Invitae RCV000700264 SCV000829012 pathogenic Brugada syndrome 2018-01-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1383*) 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 been reported in an individual referred for testing for Brugada syndrome (PMID: 20129283). ClinVar contains an entry for this variant (Variation ID: 431948). Loss-of-function variants in SCN5A are known to be pathogenic (PMID: 20129283, 22789973). For these reasons, this variant has been classified as Pathogenic.

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