ClinVar Miner

Submissions for variant NM_172362.3(KCNH1):c.2636C>T (p.Ser879Leu)

dbSNP: rs2149000783
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001880836 SCV002145937 uncertain significance not provided 2022-08-23 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 879 of the KCNH1 protein (p.Ser879Leu). This variant has not been reported in the literature in individuals affected with KCNH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1377792). 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: "Probably Damaging"; 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.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002272516 SCV002557283 uncertain significance KCNH1 associated disorder 2022-09-02 criteria provided, single submitter clinical testing A heterozygous missense variant was identified, NM_172362.2(KCNH1):c.2636C>T in exon 11 of 11 of the KCNH1 gene. This substitution is predicted to create a major amino acid change from serine to leucine at position 879 of the protein, NP_758872.1(KCNH1):p.(Ser879Leu). The serine at this position has very high conservation (100 vertebrates, UCSC), but is not situated in a known functional domain. In silico software predictions of the pathogenicity of this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is not present in the gnomAD population database. This variant has not been previously reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS).

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.