ClinVar Miner

Submissions for variant NM_014000.2(VCL):c.2444A>G (p.Lys815Arg) (rs373010557)

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
Ambry Genetics RCV000620621 SCV000736993 uncertain significance Cardiovascular phenotype 2016-06-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Erich and Hanna Klessmann Institute for Cardiovascular Research and Development,Heart and Diabetes Center North Rhine-Westphalia RCV000491755 SCV000298129 uncertain significance Dilated cardiomyopathy 1S 2016-05-01 no assertion criteria provided clinical testing
Invitae RCV000464811 SCV000548804 uncertain significance Dilated cardiomyopathy 1W 2018-10-05 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 815 of the VCL protein (p.Lys815Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs373010557, ExAC 0.003%). This variant has been reported to segregate with dilated cardiomyopathy in a single family, along with a variant of uncertain significance in MYPBC3 that was found in three of the four affected individuals (PMID: 24062880). ClinVar contains an entry for this variant (Variation ID: 45596). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038813 SCV000062491 uncertain significance not specified 2014-06-19 criteria provided, single submitter clinical testing The Lys815Arg variant in VCL has been identified in one individual with DCM who also carried a second variant of unknown significance in MYBPC3 and segregated w ith disease in 3 affected family members, 2 of whom also carried the MYBPC3 vari ant (Wells 2011 and LMM unpublished data). The Lys815Arg variant has been identi fied in 1/8600 European American chromosomes by the NHLBI Exome Sequencing Proje ct (http://evs.gs.washington.edu/EVS; dbSNP rs373010557). Lysine (Lys) at positi on 815 is highly conserved in mammals and evolutionarily distant species, sugges ting that a change at this position may not be tolerated. While VCL variants ha ve been identified in individuals with HCM as well as DCM (Olson 2002, Vasile 20 06), few studies exist and the contribution of VCL to HCM and/or DCM as well as the types of pathogenic variation have not been well established. In summary, th e clinical significance of the Lys815Arg variant is uncertain and additional stu dies are needed to fully establish its clinical significance.

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.