Submissions for variant NM_000256.3(MYBPC3):c.927-8G>A

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV002306128	SCV002599853	likely pathogenic	not provided	2022-05-03	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a damaging effect on splicing (Wood et al., 2021); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: Wood2021[Case report])
Labcorp Genetics (formerly Invitae), Labcorp	RCV005096122	SCV005803300	likely pathogenic	Hypertrophic cardiomyopathy	2024-07-02	criteria provided, single submitter	clinical testing	This sequence change falls in intron 11 of the MYBPC3 gene. It does not directly change the encoded amino acid sequence of the MYBPC3 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinical features of hypertrophic cardiomyopathy (PMID: 35508642; Invitae; Wood KA, et al. 2021. Cardiogenetics. 11:73–83). ClinVar contains an entry for this variant (Variation ID: 1723021). Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (Wood KA, et al. 2021. Cardiogenetics. 11:73–83). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.