Submissions for variant NM_000256.3(MYBPC3):c.214_215dup (p.Pro73fs)

dbSNP: rs730880362

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000156329	SCV000206047	pathogenic	Hypertrophic cardiomyopathy	2014-02-06	criteria provided, single submitter	clinical testing	The Pro73fs variant in MYBPC3 has not been previously reported in individuals wi th cardiomyopathy. Data from large population studies is insufficient to assess the frequency of this variant. This frameshift variant is predicted to alter the protein?s amino acid sequence beginning at position 73 and lead to a premature termination codon 24 amino acids downstream. This alteration is then predicted t o lead to a truncated or absent protein. Heterozygous loss of function of the MY BPC3 gene is an established disease mechanism in individuals with HCM. In summar y, this variant meets our criteria to be classified as pathogenic (http://pcpgm. partners.org/LMM) based upon the predicted impact of the variant.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149955	SCV003838291	likely pathogenic	Cardiomyopathy	2022-03-31	criteria provided, single submitter	clinical testing
Invitae	RCV000156329	SCV004428727	pathogenic	Hypertrophic cardiomyopathy	2023-01-09	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 179537). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro73Alafs*24) 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).