Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000497823 | SCV000589761 | uncertain significance | not provided | 2017-05-25 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the COL3A1 gene. The R794H variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R794H substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, the R794H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, although the R794H variant is located in the triple helical region of the COL3A1 gene, it does not affect a Glycine residue in a Gly-X-Y motif, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012). |
| Labcorp Genetics |
RCV001041011 | SCV001204605 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2019-04-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 794 of the COL3A1 protein (p.Arg794His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with COL3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 432085). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C25"). 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. |
| Mayo Clinic Laboratories, |
RCV000497823 | SCV005408945 | uncertain significance | not provided | 2023-12-27 | criteria provided, single submitter | clinical testing | PP3, PM2 |