Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158382 | SCV000208317 | pathogenic | not provided | 2020-10-08 | criteria provided, single submitter | clinical testing | Reported in association with HCM (Alfares et al., 2015; Walsh et al., 2017) and has been identified independently of additional cardiogenetic variants in other individuals referred for HCM genetic testing at GeneDx; Not observed in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Reported in ClinVar as a pathogenic variant (ClinVar Variant ID#164059; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 27532257, 25611685) |
| Invitae | RCV000151085 | SCV002243277 | pathogenic | Hypertrophic cardiomyopathy | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr959Glyfs*91) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 25611685). ClinVar contains an entry for this variant (Variation ID: 164059). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002433650 | SCV002751122 | pathogenic | Cardiovascular phenotype | 2019-08-29 | criteria provided, single submitter | clinical testing | The c.2875_2876delAC pathogenic mutation, located in coding exon 27 of the MYBPC3 gene, results from a deletion of two nucleotides at nucleotide positions 2875 to 2876, causing a translational frameshift with a predicted alternate stop codon (p.T959Gfs*91). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Color Diagnostics, |
RCV003531973 | SCV004358660 | pathogenic | Cardiomyopathy | 2021-12-07 | criteria provided, single submitter | clinical testing | This variant deletes 2 nucleotides in exon 27 of the MYBPC3 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individual(s) affected with hypertrophic cardiomyopathy (PMID: 25611685, 27532257). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MYBPC3 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Laboratory for Molecular Medicine, |
RCV000151085 | SCV000198834 | pathogenic | Hypertrophic cardiomyopathy | 2013-03-05 | no assertion criteria provided | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |