Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000794180 | SCV000933571 | pathogenic | Desmin-related myofibrillar myopathy | 2023-02-08 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2 of the DES protein (p.Ser2Ile). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects DES function (PMID: 19763525). 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. ClinVar contains an entry for this variant (Variation ID: 66414). This missense change has been observed in individuals with autosomal dominant myofibrillar myopathy (PMID: 14711882, 22153487, 25208129). |
| Athena Diagnostics | RCV000056804 | SCV004229575 | likely pathogenic | not provided | 2022-12-28 | criteria provided, single submitter | clinical testing | This variant has been identified in multiple unrelated individuals with clinical features of autosomal dominant myofibrillar myopathy. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004799771 | SCV005422092 | pathogenic | Primary familial dilated cardiomyopathy | 2024-10-25 | criteria provided, single submitter | clinical testing | Variant summary: DES c.5G>T (p.Ser2Ile) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 220124 control chromosomes. c.5G>T has been reported in the literature in multiple individuals affected with autosomal dominant myofibrillar myopathy, and has been shown to segregate with disease in at least one family (e.g., Claeys_2008, Semmler_2014, Wahbi_2012). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 18653338, 25208129, 22153487). ClinVar contains an entry for this variant (Variation ID: 66414). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Epithelial Biology; Institute of Medical Biology, |
RCV000056804 | SCV000087917 | not provided | not provided | no assertion provided | not provided |