Submissions for variant NM_000256.3(MYBPC3):c.2789del (p.Leu930fs)

dbSNP: rs876657705

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000809853	SCV000271409	pathogenic	Hypertrophic cardiomyopathy	2015-08-13	criteria provided, single submitter	clinical testing	The p.Leu930fs variant in MYBPC3 has not been previously reported in individuals with cardiomyopathy and is absent from large population studies. This variant i s predicted to cause a frameshift, which alters the protein?s amino acid sequenc e beginning at position 930 and leads to a premature termination codon 2 amino a cids downstream. This alteration is then predicted to lead to a truncated or abs ent protein. Heterozygous loss of function of the MYBPC3 gene is an established disease mechanism in individuals with HCM. In summary, this variant meets our c riteria to be classified as pathogenic for HCM in an autosomal dominant manner ( http://pcpgm.partners.org/LMM) based upon the predicted impact of the variant.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000217959	SCV000747956	pathogenic	Primary familial hypertrophic cardiomyopathy	2017-06-26	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000809853	SCV000950033	pathogenic	Hypertrophic cardiomyopathy	2024-04-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu930Argfs*2) 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: 27532257). ClinVar contains an entry for this variant (Variation ID: 228370). For these reasons, this variant has been classified as Pathogenic.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486772	SCV004239368	pathogenic	Cardiomyopathy	2022-10-05	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV005404410	SCV006069616	pathogenic	Cardiovascular phenotype	2022-06-02	criteria provided, single submitter	clinical testing