Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000685678 | SCV000813168 | uncertain significance | Hypertrophic cardiomyopathy | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1221 of the MYBPC3 protein (p.Leu1221Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 565980). 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 disruptive. 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. |
| Ambry Genetics | RCV003372801 | SCV004096180 | uncertain significance | Cardiovascular phenotype | 2023-06-22 | criteria provided, single submitter | clinical testing | The p.L1221V variant (also known as c.3661C>G), located in coding exon 33 of the MYBPC3 gene, results from a C to G substitution at nucleotide position 3661. The leucine at codon 1221 is replaced by valine, an amino acid with highly 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. |