Submissions for variant NM_000256.3(MYBPC3):c.1358dup (p.Val454fs)

dbSNP: rs727503203

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158474	SCV000208409	pathogenic	Cardiomyopathy	2011-12-07	criteria provided, single submitter	clinical testing	An insertion of a single “C” nucleotide in exon 16 of the MYBPC3 gene. The normal sequence with the base that is inserted in braces is: GCCCCC{C}TGTGC. This mutation is denoted c.1358dupC at the cDNA level or p.Val454CysfsX21 at the protein level. Although the c.1358dupC mutation in the MYBPC3 gene has not been reported previously, this mutation causes a shift in reading frame starting at codon Valine 454, changing it to a Cysteine, and creates a premature stop codon at position 21 of the new reading frame. The c.1358dupC mutation is expected to result in an abnormal, truncated protein or in absence of protein from this allele due to mRNA decay. Multiple frameshift mutations in the MYBPC3 gene have been reported in association with HCM The variant is found in HCM panel(s).
Laboratory of Genetics and Molecular Cardiology, University of São Paulo	RCV000201508	SCV000256179	likely pathogenic	Hypertrophic cardiomyopathy 4		criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Region Ostergotland	RCV000201508	SCV001984997	pathogenic	Hypertrophic cardiomyopathy 4	2020-10-27	criteria provided, single submitter	clinical testing	PVS1, PS4, PM2, PP5