ClinVar Miner

Submissions for variant NM_000218.3(KCNQ1):c.1925G>T (p.Cys642Phe)

gnomAD frequency: 0.00001  dbSNP: rs1456989889
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001843257 SCV001351956 uncertain significance Cardiac arrhythmia 2023-12-08 criteria provided, single submitter clinical testing This missense variant replaces cysteine with phenylalanine at codon 642 of the KCNQ1 protein. Computational prediction tools indicate that this variant's impact on protein structure and function is inconclusive. This variant is found within a highly conserved C-terminus region (a.a. 608-676). Rare non-truncating variants in this region have been shown to be significantly overrepresented in individuals with long QT syndrome (PMID: 32893267). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least 1 individual affected with hypertrophic cardiomyopathy (PMID: 25351510). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV002559916 SCV003476741 uncertain significance Long QT syndrome 2022-01-26 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 642 of the KCNQ1 protein (p.Cys642Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KCNQ1-related conditions. ClinVar contains an entry for this variant (Variation ID: 924413). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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