Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000620020 | SCV000740254 | uncertain significance | Cardiovascular phenotype | 2017-11-28 | criteria provided, single submitter | clinical testing | The p.V846I variant (also known as c.2536G>A), located in coding exon 25 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 2536. The valine at codon 846 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, isoleucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV001190207 | SCV001357649 | uncertain significance | Cardiomyopathy | 2023-04-20 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with isoleucine at codon 846 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYBPC3-related disorders in the literature. This variant has been identified in 4/279436 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV002531868 | SCV002956238 | uncertain significance | Hypertrophic cardiomyopathy | 2023-06-29 | criteria provided, single submitter | clinical testing | An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. ClinVar contains an entry for this variant (Variation ID: 520384). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. This variant is present in population databases (rs747774791, gnomAD 0.01%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 846 of the MYBPC3 protein (p.Val846Ile). |
| All of Us Research Program, |
RCV002531868 | SCV004839241 | uncertain significance | Hypertrophic cardiomyopathy | 2024-04-10 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with isoleucine at codon 846 of the MYBPC3 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <=0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 4/279436 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000620020 | SCV006065307 | uncertain significance | Cardiovascular phenotype | 2025-04-09 | criteria provided, single submitter | clinical testing |