ClinVar Miner

Submissions for variant NM_014000.2(VCL):c.688C>T (p.Arg230Cys) (rs139312390)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172497 SCV000051355 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Invitae RCV000227145 SCV000289921 uncertain significance Dilated cardiomyopathy 1W 2018-10-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 230 of the VCL protein (p.Arg230Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs139312390, ExAC 0.01%). This variant has not been reported in the literature in individuals with VCL-related disease. ClinVar contains an entry for this variant (Variation ID: 45620). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000038838 SCV000062516 uncertain significance not specified 2012-09-21 criteria provided, single submitter clinical testing The Arg230Cys variant in VCL has been identified in one individual with HCM by o ur laboratory, but did not segregate with disease in one affected relative. It h as been identified in 3/8600 European American chromosomes from a broad populati on by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSN P rs139312390); however, this frequency is too low to rule out a role in disease . Computational analyses (conservation, biochemical amino acid properties, Align GVGD, and SIFT) suggest that this variant may impact the protein, though this in formation is not predictive enough to determine pathogenicity. In summary, addit ional information is needed to fully assess the clinical significance of this va riant.

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