Submissions for variant NM_000256.3(MYBPC3):c.3472_3481del (p.Val1158fs)

dbSNP: rs730880675

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158403	SCV000208338	pathogenic	Cardiomyopathy	2013-08-15	criteria provided, single submitter	clinical testing	c.3472_c.3481del: p.Val1158ProfsX28 (V1158PfsX28) in exon 31 of the MYBPC3 gene (NM_000256.3). The normal sequence with the bases that are deleted in braces is: GCCC{GTCTTTATCC}CCAG. Although the c.3472_3481del mutation in the MYBPC3 gene has not been reported to our knowledge, this mutation causes a shift in reading frame starting at codon Valine 1158, changing it to a Proline, and creating a premature stop codon at position 28 of the new reading frame, denoted p.Val1158ProfsX28. 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.3472_3481del in the MYBPC3 gene is interpreted as a disease-causing mutation. The variant is found in HCM panel(s).
Invitae	RCV003748193	SCV004462867	pathogenic	Hypertrophic cardiomyopathy	2023-04-28	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: 181103). 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.Val1158Profs*28) 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).