ClinVar Miner

Submissions for variant NM_014000.2(VCL):c.2827C>G (p.Pro943Ala) (rs71579375)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172737 SCV000051511 likely benign not provided 2013-06-24 criteria provided, single submitter research
Invitae RCV000172737 SCV000289913 likely benign not provided 2018-12-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000244628 SCV000318534 likely benign Cardiovascular phenotype 2017-12-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Does not segregate with disease in family study (genes with incomplete penetrance)
GeneDx RCV000172737 SCV000536420 uncertain significance not provided 2018-11-14 criteria provided, single submitter clinical testing The P943A variant of uncertain significance in the VCL gene has been previously described in association with HCM; however, it has been reported to not segregate with disease, and at least one individual who was found to harbor P943A harbored a second cardiogenetic variant (Vasile et al., 2006; Ng et al., 2013; Lopes et al., 2015). Although P943A has also been identified in two other individuals referred for cardiomyopathy genetic testing at GeneDx, both individuals harbored additional cardiogenetic variants that likely contributed to the phenotype. In addition, P943A has been observed in 0.07% of alleles from individuals of Latino background and 0.02% of alleles from individuals of European (non-Finnish) background in large population cohorts (Lek et al., 2016). This substitution also occurs at a position that is not conserved across species. Nevertheless, P943A is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769117 SCV000900491 uncertain significance Cardiomyopathy 2017-07-13 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845310 SCV000987351 uncertain significance Familial dilated cardiomyopathy criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000172737 SCV001147984 uncertain significance not provided 2018-08-01 criteria provided, single submitter clinical testing

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.