Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000520240 | SCV000619377 | uncertain significance | not provided | 2017-07-24 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the DMD gene. The V788L variant has not been published as pathogenic or been reported as benign to our knowledge. The V788L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V788L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this substitution occurs at a position where amino acids with similar properties to valine (V) are tolerated across species, and leucine (L) is the wild-type amino acid at this position in at least one species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Moreover, missense variants represent the minority of disease-causing variants, with 65-70% of pathogenic variants in the DMD gene being exon-level deletions and duplications (Aartsma-Rus et al., 2006). |
| Labcorp Genetics |
RCV000799719 | SCV000939395 | uncertain significance | Duchenne muscular dystrophy | 2024-11-15 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 788 of the DMD protein (p.Val788Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with DMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 450763). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DMD protein function with a negative predictive value of 95%. 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 | RCV002456009 | SCV002735763 | likely benign | Cardiovascular phenotype | 2024-06-05 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Natera, |
RCV001829499 | SCV002092144 | uncertain significance | Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency | 2018-10-30 | no assertion criteria provided | clinical testing |