ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.70_71del (p.Leu24fs) (rs397508110)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182294 SCV000234597 pathogenic not provided 2019-01-11 criteria provided, single submitter clinical testing The c.451_452delCT pathogenic variant in the KCNQ1 gene has previously been reported as a homozygous variant in two siblings with Jervell-Lange Nielsen syndrome (JLNS), who each exhibited markedly prolonged QT intervals and congenital deafness (Chen et al., 1999). This case report also noted the heterozygous parents had borderline QT intervals and this variant was not detected in 100 healthy control individuals (Chen et al., 1999). The c.451_452delCT variant has subsequently been observed in one individual with autosomal dominant LQTS, and was absent in >2,600 alleles from control individuals (Kapplinger et al., 2009). This variant causes a shift in reading frame starting at codon leucine 151, changing it to a glycine, and creating a premature stop codon at position 133 of the new reading frame, denoted p.Leu151GlyfsX133. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the KCNQ1 gene have been reported in Human Gene Mutation Database in association with KCNQ1-related disorders (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.451_452delCT variant has not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
OMIM RCV000003281 SCV000023439 pathogenic Jervell and Lange-Nielsen syndrome 1 1999-03-16 no assertion criteria provided literature only

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