ClinVar Miner

Submissions for variant NM_014000.2(VCL):c.1621C>G (p.Leu541Val) (rs370229150)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000246145 SCV000317484 uncertain significance Cardiovascular phenotype 2015-06-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000645327 SCV000767070 uncertain significance Dilated cardiomyopathy 1W 2018-10-31 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 541 of the VCL protein (p.Leu541Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs370229150, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with hypertrophic cardiomyopathy (HCM) (PMID: 25351510). ClinVar contains an entry for this variant (Variation ID: 263345). 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: "Deleterious"; PolyPhen-2: "Benign"; 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769111 SCV000900484 uncertain significance Cardiomyopathy 2017-02-27 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845476 SCV000987571 uncertain significance Familial dilated cardiomyopathy criteria provided, single submitter clinical testing

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