Submissions for variant NM_000256.3(MYBPC3):c.2894_2905+4del

dbSNP: rs730880717

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158481	SCV000208416	pathogenic	Cardiomyopathy	2014-09-04	criteria provided, single submitter	clinical testing	c.2894_2905+4del in the exon 27/intron 27 junction of the MYBPC3 gene (NM_000256.3). The normal sequence with the bases that are deleted in braces is: GTGC{delAGGAGATCCTGCGTGA}gtgc. Upper case letters represent exonic sequence; lower case letters represent intronic sequence. Although c.2894_2905+4del has not been reported as a disease-causing mutation to our knowledge, this mutation results in a deletion across the junction of exon/intron 27, leading to the destruction of the natural splice donor site. The mutation is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Other splice site mutations in the MYBPC3 gene have been reported in association with HCM and DCM. Additionally, the c.2894_2905+4del mutation was not observed in approximately 6,100 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.2894_2905+4del in the MYBPC3 gene is interpreted as a disease-causing mutation. The variant is found in HCM panel(s).