ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1227-13G>A (rs397515893)

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
Blueprint Genetics RCV000788858 SCV000928127 pathogenic not provided 2018-12-18 criteria provided, single submitter clinical testing
Invitae RCV000458315 SCV000546467 pathogenic Hypertrophic cardiomyopathy 2018-11-16 criteria provided, single submitter clinical testing This sequence change falls in intron 14 of the MYBPC3 mRNA. It does not directly change the encoded amino acid sequence of the MYBPC3 protein. This variant is present in population databases (rs397515893, ExAC <0.01%). This variant has been reported to segregate with hypertrophic cardiomyopathy in two families and observed in several unrelated individuals with the same disease (PMID: 12110947, 23782526, 28797094, Invitae). ClinVar contains an entry for this variant (Variation ID: 42513). An experimental study with RNA/cDNA from an affected individual with this variant has shown that this variant causes a splicing defect that results in a frameshift and is predicted to result in a premature stop codon leading to an absent or truncated protein (PMID: 12110947). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000458315 SCV000059026 pathogenic Hypertrophic cardiomyopathy 2019-02-01 criteria provided, single submitter clinical testing The c.1227-13G>A variant in MYBPC3 has been reported in 5 individuals with hyper trophic cardiomyopathy (HCM) and segregated with disease in 3 affected individua ls from 2 families (Jaaskelainen 2002, Mendes de Almeida 2017, Nu?ez 2013, LMM d ata). It has also been identified in 2/23872 Finnish chromosomes by gnomAD (http ://gnomad.broadinstitute.org) and has been reported in ClinVar (Variation ID: 42 513). This variant is located in the 3' splice region. RNA analysis from periphe ral blood obtained from an affected individual showed that this variant introduc es a cryptic splice site leading to an insertion of 11 intronic nucleotides and subsequently a frameshift and premature termination 16 amino acids downstream (J aaskelainen 2002). This alteration is then predicted to lead to a truncated or a bsent protein. Loss of function of the MYBPC3 gene is an established disease mec hanism in autosomal dominant HCM. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HCM. ACMG/AMP Criteria applied: PVS1, PM2_Supporting, PP1, PP3, PS4_Supporting.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000624299 SCV000740368 uncertain significance not specified 2017-06-08 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.