Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158278 | SCV000208213 | likely benign | not specified | 2016-01-06 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Invitae | RCV000822463 | SCV000963265 | uncertain significance | Hypertrophic cardiomyopathy | 2022-05-11 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 140 of the MYBPC3 protein (p.Ala140Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 21750094). ClinVar contains an entry for this variant (Variation ID: 181034). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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. |
Color Diagnostics, |
RCV001179379 | SCV001344033 | uncertain significance | Cardiomyopathy | 2023-04-07 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with proline at codon 140 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 been identified in an individual affected with hypertrophic cardiomyopathy (PMID: 21750094). 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. |
Mayo Clinic Laboratories, |
RCV001507794 | SCV001713573 | uncertain significance | not provided | 2020-10-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002326897 | SCV002626624 | uncertain significance | Cardiovascular phenotype | 2020-02-14 | criteria provided, single submitter | clinical testing | The p.A140P variant (also known as c.418G>C), located in coding exon 4 of the MYBPC3 gene, results from a G to C substitution at nucleotide position 418. The alanine at codon 140 is replaced by proline, an amino acid with highly similar properties. This variant was reported in an individual with hypertrophic cardiomyopathy; however, clinical details were limited (Waldmüller S et al. Eur. J. Heart Fail., 2011 Nov;13:1185-92). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |