ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.5726A>G (p.Gln1909Arg) (rs199473326)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183131 SCV000235544 pathogenic not provided 2012-05-28 criteria provided, single submitter clinical testing p.Gln1909Arg (CAG>CGG): c.5726 A>G in exon 28 of the SCN5A gene (NM_198056.2) The Gln1909Arg mutation in the SCN5A gene has also been reported previously in one individual with LQTS, and this mutation was absent from 1,688 control alleles (Tester D et al., 2005). The NHLBI ESP Exome Variant Server reports Gln1909Arg was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Gln1909Arg results in a non-conservative amino acid substitution of a neutral, polar Glutamine with a positively charged Arginine at a residue that is conserved across species. In silico analysis predicts Gln1909Arg is probably damaging to the protein structure/function. In addition, a mutation in a nearby codon (Arg1913His) has also been reported in association with LQTS, supporting the functional importance of this region of the protein. In summary, Gln1909Arg in the SCN5A gene is interpreted as a disease-causing mutation. The variant is found in LQT panel(s).
Ambry Genetics RCV000244977 SCV000319731 uncertain significance Cardiovascular phenotype 2015-11-09 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV001190162 SCV001357588 uncertain significance Arrhythmia 2019-08-28 criteria provided, single submitter clinical testing
Invitae RCV001239705 SCV001412598 uncertain significance Brugada syndrome 2019-10-28 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 1909 of the SCN5A protein (p.Gln1909Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with long QT syndrome (PMID: 19841300). ClinVar contains an entry for this variant (Variation ID: 68008). This variant has been reported to affect SCN5A protein function (PMID: 25757662, 28734073, 28087622). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058803 SCV000090323 not provided Congenital long QT syndrome no assertion provided literature only This variant has been reported as associated with Long QT syndrome in the following publications (PMID:15840476;PMID:19841300). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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