Submissions for variant NM_000256.3(MYBPC3):c.182del (p.Gly61fs)

dbSNP: rs730880663

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158385	SCV000208320	pathogenic	not provided	2013-05-14	criteria provided, single submitter	clinical testing	Although the c.182delG mutation in the MYBPC3 gene has not been reported to our knowledge, this mutation causes a shift in reading frame starting at codon Glycine 61, changing it to an Alanine, and creating a premature stop codon at position 6 of the new reading frame, denoted p.Gly61AlafsX6. 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 addition, c.182delG 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.In summary, c.182delG in the MYBPC3 gene is interpreted as a disease-causing mutation.
Invitae	RCV001381908	SCV001580482	pathogenic	Hypertrophic cardiomyopathy	2020-02-05	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). This variant has not been reported in the literature in individuals with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 181090). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gly61Alafs*6) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product.