ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.415del (p.Leu139fs) (rs397508125)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182270 SCV000234573 pathogenic not provided 2018-04-13 criteria provided, single submitter clinical testing The c.796delC pathogenic variant in the KCNQ1 gene has been previously reported in several unrelated individuals with LQTS (Napolitano et al., 2005; Kapplinger et al., 2009). This variant has also been identified in multiple unrelated individuals referred for LQTS genetic testing at GeneDx, and appears to be segregating with disease in at least two of these individuals' families. Moreover, c.796delC has not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.796delC variant causes a shift in reading frame starting at codon leucine 266, changing it to a cysteine, and creating a premature stop codon at position 23 of the new reading frame, denoted p.L266CfsX23. 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. Furthermore, many other frameshift variants in the KCNQ1 gene have been reported in Human Gene Mutation Database in association with LQTS (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. In summary, c.796delC in the KCNQ1 gene is interpreted as a pathogenic variant.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000735818 SCV000863952 pathogenic Long QT syndrome 1 2018-12-21 criteria provided, single submitter clinical testing

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