ClinVar Miner

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

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Total submissions: 3
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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, http://exac.broadinstitute.org; 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.

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