ClinVar Miner

Submissions for variant NM_014000.2(VCL):c.1490T>C (p.Ile497Thr) (rs572757800)

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
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000678763 SCV000804942 uncertain significance Congestive heart failure 2016-03-24 no assertion criteria provided clinical testing
Invitae RCV000689300 SCV000816943 uncertain significance Dilated cardiomyopathy 1W 2018-06-08 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 497 of the VCL protein (p.Ile497Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs572757800, ExAC 0.04%). This variant has not been reported in the literature in individuals with VCL-related disease. ClinVar contains an entry for this variant (Variation ID: 505024). 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: "Benign"; Align-GVGD: "Class C45"). 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000615524 SCV000712098 uncertain significance not specified 2016-05-27 criteria provided, single submitter clinical testing The p.Ile497Thr variant in VCL has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 4/10184 African chromosomes by th e Exome Aggregation Consortium (ExAC,; dbSNP rs57 2757800). Computational prediction tools and conservation analysis do not provid e strong support for or against an impact to the protein. In summary, the clinic al significance of the p.Ile497Thr variant is uncertain.

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.