ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.123del (p.Thr42fs) (rs397508114)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001008071 SCV001167808 pathogenic not provided 2019-05-08 criteria provided, single submitter clinical testing The c.504delG pathogenic variant in the KCNQ1 gene has been reported in a 32 year-old Caucasian female diagnosed with LQTS who had an episode of syncope upon hearing the telephone ring and a QTc interval of 500 ms (Wei et al., 2000). Wei et al. (2000) also found this variant in the proband's asymptomatic 13 year-old daughter who had a QTc interval of 480 ms. The c.504delG variant causes a shift in reading frame starting at codon threonine 169, changing it to an arginine, and creating a premature stop codon at position 68 of the new reading frame, denoted p.Thr169ArgfsX68. 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. Multiple other downstream frameshift variants in the KCNQ1 gene have been reported in the 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. Furthermore, the c.504delG variant has not been observed at a significant frequency in large population cohorts (Lek et al., 2016).
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577363 SCV000679042 not provided Long QT syndrome, LQT1 subtype no assertion provided literature only

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