Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002358149 | SCV002660442 | uncertain significance | Cardiovascular phenotype | 2021-09-14 | criteria provided, single submitter | clinical testing | The p.K201R variant (also known as c.602A>G), located in coding exon 2 of the DES gene, results from an A to G substitution at nucleotide position 602. The lysine at codon 201 is replaced by arginine, 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. |
Athena Diagnostics | RCV002473371 | SCV002770671 | uncertain significance | not provided | 2022-01-26 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003776206 | SCV004569008 | uncertain significance | Desmin-related myofibrillar myopathy | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 201 of the DES protein (p.Lys201Arg). This variant is present in population databases (rs760744645, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DES-related conditions. ClinVar contains an entry for this variant (Variation ID: 1751162). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DES protein function with a negative predictive value of 80%. 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. |