Submissions for variant NM_000256.3(MYBPC3):c.275_276del (p.Leu92fs)

dbSNP: rs1057517766

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413465	SCV000490631	likely pathogenic	not provided	2017-01-24	criteria provided, single submitter	clinical testing	Although the c.275_276delTC variant in the MYBPC3 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon Leucine 92, changing it to a Glutamine, and creating a premature stop codon at position 20 of the new reading frame, denoted p.Leu92QfsX20. This variant 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 variants in the MYBPC3 gene have been reported in HGMD in association with HCM (Stenson P et al., 2014). In summary, c.275_276delTC in the MYBPC3 gene is interpreted as a pathogenic variant.
Invitae	RCV003586177	SCV004310178	pathogenic	Hypertrophic cardiomyopathy	2023-07-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu92Glnfs*20) 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. ClinVar contains an entry for this variant (Variation ID: 372417). For these reasons, this variant has been classified as Pathogenic.