ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.1705C>G (p.Arg569Gly) (rs199473576)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183172 SCV000235589 uncertain significance not provided 2016-12-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN5A gene. The R569G variant has been published in one patient referred for LQTS testing (Kapplinger et al., 2015); however, additional clinical information was not provided. Additionally, functional studies by Kapplinger et al. (2015) suggest a deleterious effect of this variant, but additional studies are needed to validate the functional effect of this variant. A missense variant at the same residue (R569W) has been reported in the Human Gene Mutation Database (Stenson et al., 2014), however, the pathogencity of this variant has not been definitively determined. Nevertheless, the R569G variant was not observed in approximately 6,200 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 R569G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where only amino acids with similar properties to Arginine are tolerated across species. Finally, in silico analysis predicts this variant is probably damaging to the protein structure/function.
Color Health, Inc RCV001182790 SCV001348371 uncertain significance Arrhythmia 2019-12-31 criteria provided, single submitter clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000656205 SCV000678399 likely pathogenic Wolff-Parkinson-White pattern 2017-07-14 no assertion criteria provided research This variant was identified in an individual with Wolff-Parkinson-White syndrome

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