Submissions for variant NM_000256.3(MYBPC3):c.2992C>T (p.Gln998Ter)

dbSNP: rs11570112

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158203	SCV000208138	pathogenic	not provided	2014-04-21	criteria provided, single submitter	clinical testing	This mutation is denoted p.Gln998Stop (CAG>TAG): c.2992 C>T in exon 28 of the MYBPC3 gene (NM_000256.3). The Q998X mutation in the MYBPC3 gene has been reported in at least one patient with HCM (Millat G et al., 2010). Millat et al. (2010) report that the Q998X mutation was not seen in 200 control individuals. Furthermore, the Q998X mutation was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, Q998X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense mutations in the MYBPC3 gene have been reported in association with HCM. In summary, Q998X in the MYBPC3 gene is interpreted as a disease-causing mutation. The variant is found in HCM panel(s).
Invitae	RCV001388605	SCV001589662	pathogenic	Hypertrophic cardiomyopathy	2020-02-19	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 variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 20624503). ClinVar contains an entry for this variant (Variation ID: 180993). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln998*) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product.