ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2113dup (p.Thr705fs)

dbSNP: rs397515948
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000204303 SCV000059113 pathogenic Hypertrophic cardiomyopathy 2010-09-09 criteria provided, single submitter clinical testing The Thr705fs variant has not been reported in the literature. This variant is p redicted to cause a frameshift, which alters the protein's amino acid sequence b eginning at codon 705 and leads to a premature stop codon two amino acids downst ream. This alteration is then predicted to lead to a truncated or absent protei n. Loss of function is an established mechanism of disease for the MYBPC3 gene, which makes it highly likely that the Thr705fs variant is pathogenic.
Invitae RCV000204303 SCV000259647 pathogenic Hypertrophic cardiomyopathy 2015-07-29 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Truncating variants in MYBPC3 are known to be pathogenic (PMID: 19574547). This sequence change inserts 1 nucleotide in exon 22 of the MYBPC3 mRNA (c.2113dupA), causing a frameshift at codon 705. This creates a premature translational stop signal (p.Thr705Asnfs*3) and is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV003162299 SCV003911239 pathogenic Cardiovascular phenotype 2021-06-10 criteria provided, single submitter clinical testing The c.2113dupA pathogenic mutation, located in coding exon 22 of the MYBPC3 gene, results from a duplication of A at nucleotide position 2113, causing a translational frameshift with a predicted alternate stop codon (p.T705Nfs*3). This alteration has been reported in association with hypertrophic cardiomyopathy (HCM) (Olivotto I et al. Mayo Clin Proc, 2008 Jun;83:630-8; Page SP et al. Circ Cardiovasc Genet, 2012 Apr;5:156-66; Walsh R et al. Genet Med, 2017 02;19:192-203). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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.