Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000618443 | SCV000737252 | uncertain significance | Cardiovascular phenotype | 2021-11-15 | criteria provided, single submitter | clinical testing | The p.I867V variant (also known as c.2599A>G), located in coding exon 25 of the MYBPC3 gene, results from an A to G substitution at nucleotide position 2599. The isoleucine at codon 867 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV000769318 | SCV000900696 | uncertain significance | Cardiomyopathy | 2017-02-16 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001210902 | SCV001382414 | uncertain significance | Hypertrophic cardiomyopathy | 2023-05-16 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 519160). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. This variant is present in population databases (rs768339148, gnomAD 0.007%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 867 of the MYBPC3 protein (p.Ile867Val). |
Revvity Omics, |
RCV003133405 | SCV003817154 | uncertain significance | not provided | 2019-11-14 | criteria provided, single submitter | clinical testing |