ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.927-10C>A (rs201078659)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000628867 SCV000749775 likely pathogenic Hypertrophic cardiomyopathy 2018-09-28 criteria provided, single submitter clinical testing This sequence change falls in intron 11 of the MYBPC3 gene. It does not directly change the encoded amino acid sequence of the MYBPC3 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with hypertrophic cardiomyopathy (PMID: 25611685). ClinVar contains an entry for this variant (Variation ID: 42805). Experimental studies have shown that this intronic change leads to aberrant splicing resulting in exon 12 skipping (PMID: 28679633). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000628867 SCV000059332 likely pathogenic Hypertrophic cardiomyopathy 2019-01-31 criteria provided, single submitter clinical testing The c.927-10C>A variant in MYBPC3 has been identified in 3 individuals with HCM and segregated with disease in 4 affected relatives from 2 families (LMM data). It was absent from large population studies. This variant is located in the 3' s plice region. An in vitro splicing assay demonstrates that this variant impacts splicing (Ito 2017). Variants that impact splicing and other loss-of-function va riants in MYBPC3 are a common cause of HCM. In summary, although additional stu dies are required to fully establish its clinical significance, this variant mee ts criteria to be classified as likely pathogenic for autosomal dominant HCM. AC MG/AMP Criteria applied: PS3_Moderate, PM2, PS4_Supporting, PP1.

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