ClinVar Miner

Submissions for variant NM_000218.2(KCNQ1):c.1747C>T (p.Arg583Cys) (rs17221854)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057628 SCV000089147 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:10973849;PMID:11997281;PMID:14760488). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Fulgent Genetics,Fulgent Genetics RCV000762837 SCV000893196 likely pathogenic Atrial fibrillation, familial, 3; Beckwith-Wiedemann syndrome; Long QT syndrome 1; Jervell and Lange-Nielsen syndrome 1; Short QT syndrome 2 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000182219 SCV000234522 pathogenic not provided 2013-10-18 criteria provided, single submitter clinical testing p.Arg583Cys (R583C) CGC>TGC: c.1747 C>T in exon 15 of the KCNQ1 gene (NM_000218.2). The Arg583Cys mutation in the KCNQ1 gene has been reported in one individual with LQTS and it was absent from more than 400 control chromosomes (Splawski I et al., 2000). Furthermore, the Arg583Cys mutation was not observed 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. One in vitro study indicated Arg583Cys resulted a mild functional change in the ion current of the potassium channel (Yang P et al., 2002). Arg583Cys results in a semi-conservative amino acid substitution of a positively charged Arginine with a neutral, polar Cysteine at a position that is conserved in mammals. Mutations in this residue (Arg583His) and in nearby residues (Val576Leu, Asn586Asp) have been reported in association with LQTS, further supporting the functional importance of this region of the protein. The variant is found in LQT panel(s).
OMIM RCV000003291 SCV000023449 pathogenic Long QT syndrome 1 2002-04-23 no assertion criteria provided literature only
OMIM RCV000003292 SCV000023450 risk factor Acquired susceptibility to long QT syndrome 1 2002-04-23 no assertion criteria provided literature only

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