Submissions for variant NM_000256.3(MYBPC3):c.2604del (p.Ser871fs)

dbSNP: rs730880655

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158371	SCV000208306	pathogenic	Cardiomyopathy	2014-08-14	criteria provided, single submitter	clinical testing	c.2604delT: p.Ser871AlafsX8 (S871AfsX8) in exon 26 of the MYBPC3 gene (NM_000256.3) The normal sequence with the base that is deleted in braces is: cagG[T]CCCC. Uppercase letters represent exonic sequence; lower case letters represent intronic sequence. Although the c.2604delT mutation in the MYBPC3 gene has not been reported to our knowledge, this mutation causes a shift in reading frame starting at codon Serine 871, changing it to an Alanine, and creating a premature stop codon at position 8 of the new reading frame, denoted p.Ser871AlafsX8 . 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 hypertrophic cardiomyopathy. In summary, c.2604delT in the MYBPC3 gene is interpreted as a disease-causing mutation. The variant is found in HCM panel(s).
Invitae	RCV001219377	SCV001391312	pathogenic	Hypertrophic cardiomyopathy	2019-05-27	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 frameshift has been observed in individuals affected with hypertrophic cardiomyopathy (PMID: 25351510, 27600940, 28615295). ClinVar contains an entry for this variant (Variation ID: 181082). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser871Alafs*8) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product.