ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.3724G>A (p.Asp1242Asn) (rs199473599)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618887 SCV000737716 uncertain significance Cardiovascular phenotype 2016-09-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058595 SCV000090115 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:20129283). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Color RCV000777722 SCV000913668 likely benign Arrhythmia 2018-08-31 criteria provided, single submitter clinical testing
GeneDx RCV000455383 SCV000565535 uncertain significance not specified 2016-08-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN5A gene. The D1243N variant has been reported previously in one individual with type 2 Brugada syndrome and in five individuals referred for Brugada syndrome genetic testing; segregation and functional data was not provided (Selga et al., 2015; Kapplinger et al., 2010). This variant has also been reported in other individuals tested for Brugada syndrome at GeneDx. The D1243N variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D1243N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Furthermore, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function.However, additional evidence is needed to determine whether this variant is pathogenic or benign.
Illumina Clinical Services Laboratory,Illumina RCV000778920 SCV000915331 uncertain significance Brugada syndrome 1 2017-04-27 criteria provided, single submitter clinical testing The SCN5A c.3727G>A (p.Asp1243Asn) missense variant has been reported in at least three studies in which it is found in a total of 11 patients with Brugada syndrome including in three in a compound heterozygous state, and in eight in a heterozygous state (four of whom are related) (Kapplinger J et al 2010; Chockalingam P et al 2012; Selga E et al 2015). The second variant in the compound heterozygous patients is either a frameshift variant or a known pathogenic missense variant. The p.Asp1243Asn variant shows segregation in one family. The p.Asp1243Asn variant was absent from 1600 controls and is reported at a frequency of 0.00018 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the evidence, the p.Asp1243Asn variant is classified as a variant of unknown significance but suspicious for pathogenicity for Brugada syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000058595 SCV000760369 likely benign Brugada syndrome 2017-12-12 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000455383 SCV000540275 uncertain significance not specified 2016-04-25 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 5 probands from 1 paper, no segs in HGMD; ExAC: 12/66724 European chromosomes

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