ClinVar Miner

Submissions for variant NM_000238.4(KCNH2):c.3410C>A (p.Ser1137Tyr)

dbSNP: rs1413026629
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001240613 SCV001413578 uncertain significance Long QT syndrome 2020-01-27 criteria provided, single submitter clinical testing 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. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with KCNH2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with tyrosine at codon 1137 of the KCNH2 protein (p.Ser1137Tyr). The serine residue is weakly conserved and there is a large physicochemical difference between serine and tyrosine.
Ambry Genetics RCV002451585 SCV002614373 uncertain significance Cardiovascular phenotype 2020-02-27 criteria provided, single submitter clinical testing The p.S1137Y variant (also known as c.3410C>A), located in coding exon 15 of the KCNH2 gene, results from a C to A substitution at nucleotide position 3410. The serine at codon 1137 is replaced by tyrosine, an amino acid with dissimilar properties, and is located in the C-terminal region of the protein. This amino acid position is highly 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.
Color Diagnostics, LLC DBA Color Health RCV003591848 SCV004357528 uncertain significance Cardiac arrhythmia 2021-08-31 criteria provided, single submitter clinical testing This missense variant replaces serine with tyrosine at codon 1137 of the KCNH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.