Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000619147 | SCV000736689 | pathogenic | Cardiovascular phenotype | 2018-05-02 | criteria provided, single submitter | clinical testing | The c.2258dupT pathogenic mutation, located in coding exon 23 of the MYBPC3 gene, results from a duplication of T at nucleotide position 2258, causing a translational frameshift with a predicted alternate stop codon (p.K754Efs*79). This alteration was previously detected in a subset of individuals with increased left ventricular wall thickness from a community-based cohort, and in a hypertrophic cardiomyopathy cohort, though details were limited (Morita H et al. Circulation. 2006;113:2697-705 (reported as 'T insertion at nt 2259'); Cecconi M et al. Int J Mol Med. 2016;38:1111-24). 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. |
| Invitae | RCV001868103 | SCV002241002 | pathogenic | Hypertrophic cardiomyopathy | 2022-10-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys754Glufs*79) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). This variant is present in population databases (rs774521272, gnomAD 0.003%). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 518947). This variant is also known as Val753fs. This premature translational stop signal has been observed in individual(s) with MYBPC3-related conditions (PMID: 16754800, 27600940). |