Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003077014 | SCV003455278 | uncertain significance | Desmin-related myofibrillar myopathy | 2024-01-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 237 of the DES protein (p.Ala237Val). This variant is present in population databases (rs374144840, gnomAD 0.0009%). 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: 2147095). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DES protein function. 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 | RCV003274194 | SCV004004404 | uncertain significance | Cardiovascular phenotype | 2023-05-27 | criteria provided, single submitter | clinical testing | The p.A237V variant (also known as c.710C>T), located in coding exon 3 of the DES gene, results from a C to T substitution at nucleotide position 710. The alanine at codon 237 is replaced by valine, an amino acid with similar properties. This alteration has been reported in a sudden infant death syndrome cohort with limited clinical details and additional alterations in other cardiac-related genes identified (Santori M et al. Arch Dis Child, 2015 Oct;100:952-6). This amino acid position is highly 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. |