Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000035680 | SCV000059331 | likely benign | not specified | 2015-04-09 | criteria provided, single submitter | clinical testing | c.926+8C>T in intron 11 of MYBPC3: This variant is not expected to have clinical significance because it is not located in the conserved region of the splicing consensus sequence. It has been identified in 33/62508 European chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs3 77595584). |
Invitae | RCV001081892 | SCV000558148 | likely benign | Hypertrophic cardiomyopathy | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000625028 | SCV000743567 | benign | Hypertrophic cardiomyopathy 4 | 2017-06-27 | criteria provided, single submitter | clinical testing | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000625028 | SCV000744861 | benign | Hypertrophic cardiomyopathy 4 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000625028 | SCV001265734 | uncertain significance | Hypertrophic cardiomyopathy 4 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Laboratory Services, |
RCV001108497 | SCV001265735 | benign | Left ventricular noncompaction 10 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
CHEO Genetics Diagnostic Laboratory, |
RCV001170204 | SCV001332756 | likely benign | Cardiomyopathy | 2023-04-03 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000457720 | SCV001883513 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000035680 | SCV002765994 | likely benign | not specified | 2023-11-07 | criteria provided, single submitter | clinical testing | Variant summary: MYBPC3 c.926+8C>T alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00071 in 1586860 control chromosomes, predominantly at a frequency of 0.00084 within the Non-Finnish European subpopulation in the gnomAD database, including 2 homozygotes. This frequency is close the maximum estimated for a pathogenic variant in MYBPC3 suggesting a benign role. c.926+8C>T has been reported in the literature in individuals affected with Hypertrophic Cardiomyopathy. These reports do not provide unequivocal conclusions about association of the variant with Hypertrophic Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 23782526). Eight submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified as benign/likely benign (n=7) and VUS (n=1). Based on the evidence outlined above, the variant was classified as likely benign. |
Clinical Genetics, |
RCV000035680 | SCV001925100 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000457720 | SCV001959527 | likely benign | not provided | no assertion criteria provided | clinical testing |