Submissions for variant NM_000256.3(MYBPC3):c.2214del (p.Glu739fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV004987276	SCV005455739	pathogenic	Cardiovascular phenotype	2024-09-30	criteria provided, single submitter	clinical testing	The c.2214delC pathogenic mutation, located in coding exon 23 of the MYBPC3 gene, results from a deletion of one nucleotide at nucleotide position 2214, causing a translational frameshift with a predicted alternate stop codon (p.E739Rfs*15). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005107561	SCV005764805	pathogenic	Hypertrophic cardiomyopathy	2024-08-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu739Argfs*15) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.