ClinVar Miner

Submissions for variant NM_000218.3(KCNQ1):c.1379G>A (p.Gly460Asp)

gnomAD frequency: 0.00003  dbSNP: rs770410327
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001842728 SCV001342824 uncertain significance Cardiac arrhythmia 2022-12-06 criteria provided, single submitter clinical testing This missense variant replaces glycine with aspartic acid at codon 460 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/248988 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.
GeneDx RCV001773422 SCV001994105 uncertain significance not provided 2020-09-16 criteria provided, single submitter clinical testing Reported in a patient with sudden arrhythmic death syndrome (SADS) (Raju et al., 2019); however, specific clinical information was not provided; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 919916; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31337358)
All of Us Research Program, National Institutes of Health RCV004006473 SCV004836434 uncertain significance Long QT syndrome 2024-03-24 criteria provided, single submitter clinical testing This missense variant replaces glycine with aspartic acid at codon 460 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with sudden arrhythmic death syndrome (PMID: 31337358) and in another individual affected with sudden unexplained death in childhood (SUDC) (PMID: 37589201). This variant has been identified in 3/248988 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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