ClinVar Miner

Submissions for variant NM_014000.2(VCL):c.32G>A (p.Ser11Asn) (rs777811020)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000645313 SCV000767056 uncertain significance Dilated cardiomyopathy 1W 2017-09-11 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 11 of the VCL protein (p.Ser11Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs777811020, ExAC 0.1%). This variant has not been reported in the literature in individuals with VCL-related disease. 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: "Probably Damaging"; 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.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000786269 SCV000925021 uncertain significance not provided 2017-10-04 no assertion criteria provided provider interpretation VCL Ser11Asn c.32G>A, exon 1 (NM_014000.2, hg19 chr10-75757997-G-A) SCICD Classification: We do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). The rationale for this assessment is: lack of gene-level evidence, lack of case data, frequency of the variant in an ethnicity-matched population. We have seen this variant in a person with HCM. Gene-level evidence: There is limited gene-level evidence linking this gene to HCM. Case data (does not include this patient): none (10/5/2017). Cases in the literature: none reported. Segregation data: none reported. Functional data: none. In silico data (missense variants only): Per the test report, "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: "Probably Damaging"; Align-GVGD: "Class C0")." Conservation data: The serine at codon 11 is conserved across all aligned vertebrates in the UCSC browser. Neighboring amino acids are conserved. Nearby pathogenic variants at this codon or neighboring codons: Another variant affecting the same codon (Ser11Gly, c.31A>G) was listed in ClinVar as a variant of uncertain significance by LMM. No case data provided. Population data: Highest MAF in East Asian population: 0.06%. The variant was reported online in 10 of 120,993 individuals (MAF: 0.004%) in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Ashkenazi, Latino descent. Specifically, the variant was observed in 10 of 8,548 individuals of East Asian descent (MAF=0.06%). The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease.

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.