Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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. |