ClinVar Miner

Submissions for variant NM_014000.2(VCL):c.2046A>T (p.Leu682Phe) (rs565398652)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000253826 SCV000319936 uncertain significance Cardiovascular phenotype 2015-07-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769114 SCV000900488 uncertain significance Cardiomyopathy 2017-10-03 criteria provided, single submitter clinical testing
Center for Human Genetics,University of Leuven RCV000497573 SCV000579544 uncertain significance Hypertrophic cardiomyopathy 2017-02-09 criteria provided, single submitter clinical testing ACMG score unknown significance
Invitae RCV000645322 SCV000767065 uncertain significance Dilated cardiomyopathy 1W 2017-08-17 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 682 of the VCL protein (p.Leu682Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs565398652, ExAC 0.01%). This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 27930701). ClinVar contains an entry for this variant (Variation ID: 166551). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000152648 SCV000201990 uncertain significance not specified 2014-02-28 criteria provided, single submitter clinical testing The Leu682Phe variant in VCL has not been previously reported in individuals wit h cardiomyopathy or in large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the clinical s ignificance of the variant.

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