Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000806472 | SCV000946475 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2020-11-24 | criteria provided, single submitter | clinical testing | 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. 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 C0"). This variant has not been reported in the literature in individuals with COL3A1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 117 of the COL3A1 protein (p.Pro117Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. |
| Gene |
RCV001759543 | SCV001996378 | uncertain significance | not provided | 2020-04-23 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar (ClinVar Variant ID# 651172; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); Not located in the triple helical region, where the majority of pathogenic missense variants occur (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |