ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.926+4A>G

dbSNP: rs397516081
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035679 SCV000059330 uncertain significance not specified 2020-10-10 criteria provided, single submitter clinical testing The c.926+4A>G variant in MYBPC3 has been reported in one individual with dilated cardiomyopathy (DCM; Ito 2017 PMID: 28679633) and was absent from large population studies. This variant is located in the 5' splice region. Computational tools predict a splicing impact and functional studies using a cell-based minigene splicing assay provide some evidence that this variant impacts splicing (Ito 2017 PMID: 28679633). In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3, PS3_Supporting.
GeneDx RCV001556831 SCV001778480 uncertain significance not provided 2020-10-02 criteria provided, single submitter clinical testing Reported in association with cardiomyopathy (Ito et al., 2017); however, additional clinical information was not provided; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 28679633)
Labcorp Genetics (formerly Invitae), Labcorp RCV001852726 SCV002165936 uncertain significance Hypertrophic cardiomyopathy 2021-08-12 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. It affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs397516081, ExAC 0.009%). This variant has been observed in individual(s) with dilated cardiomyopathy (PMID: 28679633). ClinVar contains an entry for this variant (Variation ID: 42803). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (PMID: 28679633). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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