ClinVar Miner

Submissions for variant NM_000218.3(KCNQ1):c.1348G>A (p.Glu450Lys)

gnomAD frequency: 0.00001  dbSNP: rs148266527
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001298493 SCV001487551 benign Long QT syndrome 2022-12-06 criteria provided, single submitter clinical testing
GeneDx RCV001567242 SCV001790893 likely benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV002380002 SCV002694882 uncertain significance Cardiovascular phenotype 2022-08-24 criteria provided, single submitter clinical testing The p.E450K variant (also known as c.1348G>A), located in coding exon 10 of the KCNQ1 gene, results from a G to A substitution at nucleotide position 1348. The glutamic acid at codon 450 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in a sudden unexplained death cohort; however, clinical details were limited (Huang J et al. J Forensic Sci, 2015 Mar;60:351-6). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV001298493 SCV004826565 uncertain significance Long QT syndrome 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 450 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 KCNQ1-related disorders in the literature. This variant has been identified in 2/250152 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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