ClinVar Miner

Submissions for variant NM_014000.3(VCL):c.854G>A (p.Arg285His)

gnomAD frequency: 0.00001  dbSNP: rs397517246
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000038840 SCV000062518 uncertain significance not specified 2012-02-07 criteria provided, single submitter clinical testing The Arg285His variant (VCL) has not been reported in the literature, but has bee n identified in one proband with HCM (this individual's son) by our laboratory. Arginine (Arg) at position 285 is not completely conserved across different spec ies, increasing the likelihood that a change would be tolerated. Computational a nalyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) also suggest that the Arg285His variant may not impact the protein, though this info rmation is not predictive enough to rule out pathogenicity. Variants in the VCL gene have been found in individuals with HCM as well as DCM (Olson 2002, Vasile 2006). However, the number of studies is still small and the contribution of VCL to HCM and DCM, as well as the types of variants that cause disease, have not b een well established. Additional information is needed to fully assess the clini cal significance of this variant.
Invitae RCV001059935 SCV001224590 uncertain significance Dilated cardiomyopathy 1W 2022-08-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 285 of the VCL protein (p.Arg285His). This variant is present in population databases (rs397517246, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with VCL-related conditions. ClinVar contains an entry for this variant (Variation ID: 45621). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV004678599 SCV005179528 likely benign Cardiovascular phenotype 2024-04-26 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Breakthrough Genomics, Breakthrough Genomics RCV004691729 SCV005190853 uncertain significance not provided criteria provided, single submitter not provided

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.