ClinVar Miner

Submissions for variant NM_000218.3(KCNQ1):c.1345G>A (p.Glu449Lys)

gnomAD frequency: 0.00004  dbSNP: rs372583676
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001843269 SCV001352187 uncertain significance Cardiac arrhythmia 2023-04-03 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 449 of the KCNQ1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). A functional study in transfected CHO cells has shown that this variant may not impact KCNQ1 protein function (PMID: 34930020). This variant has been reported in an individual affected with mild syncope (PMID: 34930020). This variant has been identified in 7/281818 chromosomes 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001314649 SCV001505188 benign Long QT syndrome 2023-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002379717 SCV002695105 likely benign Cardiovascular phenotype 2023-12-07 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
All of Us Research Program, National Institutes of Health RCV001314649 SCV004836422 uncertain significance Long QT syndrome 2023-05-16 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 449 of the KCNQ1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). A functional study in transfected CHO cells has shown that this variant may not impact KCNQ1 protein function (PMID: 34930020). This variant has been reported in an individual affected with mild syncope (PMID: 34930020). This variant has been identified in 7/281818 chromosomes 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.

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