ClinVar Miner

Submissions for variant NM_000218.3(KCNQ1):c.1032G>C (p.Ala344=)

dbSNP: rs1800171
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182160 SCV000234463 pathogenic not provided 2013-07-26 criteria provided, single submitter clinical testing p.Ala344Ala (GCG>GCC): c.1032 G>C in exon 7 of the KCNQ1 gene (NM_000218.2). The c.1032 G>C mutation in the KCNQ1 gene has been reported to co-segregate with a LQTS phenotype in one family (Murray A et al., 1999). The c.1032 G>C mutation changes the last nucleotide in exon 7 of the KCNQ1 gene, which affects the donor splice site and results in exon skipping (Murray A et al., 1999). Furthermore, a different nucleotide change at the same codon (c.1032 G>A, Ala344Ala) also has been reported to affect the donor splice site, and it has been reported in association with LQTS (Murray A et al., 1999). The c.1032 G>C 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.In summary, c.1032 G>C in the KCNQ1 gene is interpreted as a disease-causing mutation. The variant is found in LQT panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV005089428 SCV005835244 pathogenic Long QT syndrome 2024-09-20 criteria provided, single submitter clinical testing This sequence change affects codon 344 of the KCNQ1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the KCNQ1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinical features of Jervell and Lange-Nielsen syndrome and/or long QT syndrome (PMID: 10477533, 30036649, 31737537). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 52939). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exons 7-8 or exon 8, but is expected to preserve the integrity of the reading-frame (PMID: 10477533). For these reasons, this variant has been classified as Pathogenic.

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