Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000619303 | SCV000735730 | uncertain significance | Cardiovascular phenotype | 2023-02-27 | criteria provided, single submitter | clinical testing | The p.P214L variant (also known as c.641C>T), located in coding exon 1 of the MYPN gene, results from a C to T substitution at nucleotide position 641. The proline at codon 214 is replaced by leucine, an amino acid with 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. |
| Labcorp Genetics |
RCV001860363 | SCV002210380 | uncertain significance | Dilated cardiomyopathy 1KK | 2021-09-26 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 214 of the MYPN protein (p.Pro214Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MYPN-related conditions. ClinVar contains an entry for this variant (Variation ID: 518616). 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. |