Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003168176 | SCV003857399 | uncertain significance | Cardiovascular phenotype | 2022-12-23 | criteria provided, single submitter | clinical testing | The p.M1052T variant (also known as c.3155T>C), located in coding exon 29 of the MYBPC3 gene, results from a T to C substitution at nucleotide position 3155. The methionine at codon 1052 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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. |
| Labcorp Genetics |
RCV003748463 | SCV004483965 | uncertain significance | Hypertrophic cardiomyopathy | 2023-06-02 | 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. This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1052 of the MYBPC3 protein (p.Met1052Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 2448099). 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. |
| All of Us Research Program, |
RCV003748463 | SCV004817203 | uncertain significance | Hypertrophic cardiomyopathy | 2023-02-24 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with threonine at codon 1052 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 not been identified 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. |