Submissions for variant NM_000256.3(MYBPC3):c.453del (p.Asp151fs)

dbSNP: rs730880679

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158412	SCV000208347	pathogenic	not provided	2013-05-10	criteria provided, single submitter	clinical testing	The c.453delT mutation in the MYBPC3 gene has not been reported to our knowledge. This mutation was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.453delT mutation causes a shift in reading frame starting at codon Aspartic acid 151, changing it to a Glutamic acid, and creating a premature stop codon at position 8 of the new reading frame, denoted p.Asp151GlufsX8. This mutation is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift mutations in the MYBPC3 gene have been reported in association with HCM. In summary, c.453delT in the MYBPC3 gene is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001385759	SCV001585721	pathogenic	Hypertrophic cardiomyopathy	2021-09-17	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Asp151Glufs*8) 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 (ExAC no frequency). This variant has not been reported in the literature in individuals with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 181107).