ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3664G>T (p.Gly1222Ter)

dbSNP: rs730880598
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158250 SCV000208185 pathogenic not provided 2017-08-02 criteria provided, single submitter clinical testing The G1222X variant in the MYBPC3 gene has not been reported as a pathogenic or benign variant to our knowledge. However, G1222X has been previously identified in another individual referred for HCM testing at GeneDx. This variant was not observed in either the Exome Aggregation Consortium or approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G1222X pathogenic variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Many other nonsense variants in the MYBPC3 gene have been reported in HGMD in association with HCM (Stenson et al., 2014). In summary, G1222X in the MYBPC3 gene is interpreted as a pathogenic variant.
Invitae RCV001850211 SCV002159723 pathogenic Hypertrophic cardiomyopathy 2021-04-05 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 181016). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gly1222*) 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).

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