ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.535G>A (p.Gly179Arg) (rs120074181)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182132 SCV000234435 pathogenic not provided 2017-04-28 criteria provided, single submitter clinical testing The Gly306Arg mutation in the KCNQ1 gene has been reported multiple times in association with LQTS (Zareba W et al. 2003; Kapplinger J et al., 2009). Zareba et al. identified Gly306Arg in 17 individuals from a cohort of 55 families with LQTS, and Kapplinger J et al. identified it in two other unrelated individuals with LQTS. Collectively, these studies did not identify Gly306Arg in more than 2,600 control alleles and the NHLBI ESP Exome Variant Server reports Gly306Arg was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Functional studies report Gly306Arg results in a reduction of the channel current by a dominant negative effect (Wang Z et al., 1999; Li R et al., 2001). Gly306Arg results in a non-conservative amino acid substitution of a non-polar Glycine residue with a positively charged Arginine residue. Furthermore, mutations in the same residue (Gly306Val) and nearby residues (Leu303Pro, Trp304Arg, Trp305Arg, Trp305Ser, Val307Leu) have been reported in association with LQTS, further supporting the functional importance of this region of the protein. In summary, Gly306Arg in the KCNQ1 gene is interpreted as a disease-causing mutation.
OMIM RCV000003262 SCV000023420 pathogenic Long QT syndrome 1 1996-01-01 no assertion criteria provided literature only
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057797 SCV000089316 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:10376919;PMID:8528244;PMID:19716085;PMID:14678125;PMID:15234419;PMID:17470695;PMID:11351021). 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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