Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001767123 | SCV001990157 | uncertain significance | not provided | 2019-05-29 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat. Although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease (Stenson et al., 2014); Not observed in large population cohorts (Lek et al., 2016) |
Labcorp Genetics |
RCV002032845 | SCV002293764 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2021-03-12 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with clinical features of COL3A1-related conditions (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 242 of the COL3A1 protein (p.Arg242Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. 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 COL3A1 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. |
Genome Diagnostics Laboratory, |
RCV002276881 | SCV002565658 | uncertain significance | Ehlers-Danlos syndrome | 2021-05-07 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV002032845 | SCV004829645 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2023-05-16 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glycine at codon 242 of the COL3A1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with COL3A1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |