ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3224C>G (p.Thr1075Ser) (rs150786409)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519370 SCV000617922 uncertain significance not provided 2015-12-07 criteria provided, single submitter clinical testing A novel variant of uncertain significance has been identified in the MYBPC3 gene. The c.3224 C>G (T1075S) variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. Although this variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, the 1000 Genomes Project reports T1075S was observed in approximately 0.1% alleles from individuals of European background. While the c.3224 C>G variant results in a conservative amino acid substitution (T1075S), in silico splice prediction programs predict this variant may result in aberrant gene splicing by creating a cryptic donor splice site. However, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined. In addition, this substitution occurs at a nucleotide that is not conserved across species. Nevertheless, multiple splicing variants in the MYBPC3 gene and missense variants in nearby residues (R1073P, G1079D) have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769311 SCV000900689 uncertain significance Cardiomyopathy 2016-04-26 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV001256771 SCV001433215 uncertain significance Dilated cardiomyopathy 1A 2020-02-29 criteria provided, single submitter clinical testing

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