Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000215999 | SCV000271410 | pathogenic | Hypertrophic cardiomyopathy | 2015-04-01 | criteria provided, single submitter | clinical testing | The p.Asn1171fs variant in MYBPC3 has not been previously identified in individu als with cardiomyopathy and was absent from large population studies. This varia nt is predicted to cause a frameshift, which alters the protein?s amino acid seq uence beginning at position 1171 and leads to a premature termination codon 18 a mino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the MYBPC3 gene is an establ ished disease mechanism in cardiomyopathy. In summary, this variant meets our cr iteria to be classified as pathogenic for HCM in an autosomal dominant manner (h ttp://www.partners.org/personalizedmedicine/LMM). |
| Invitae | RCV000215999 | SCV001379673 | pathogenic | Hypertrophic cardiomyopathy | 2021-11-01 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn1171Thrfs*18) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 26914223). ClinVar contains an entry for this variant (Variation ID: 228371). For these reasons, this variant has been classified as Pathogenic. |