Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000680211 | SCV001204736 | pathogenic | Ehlers-Danlos syndrome, type 4 | 2023-05-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 COL3A1 protein function. ClinVar contains an entry for this variant (Variation ID: 561178). This missense change has been observed in individuals with clinical features of vascular Ehlers-Danlos syndrome (PMID: 30837697; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 451 of the COL3A1 protein (p.Glu451Lys). |
| Gene |
RCV001771925 | SCV001994642 | uncertain significance | not provided | 2019-03-18 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); Occurs in the triple helical domain at the X 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 X position is not a common mechanism of disease (Stenson et al., 2014); Other COL3A1 variants that result in a X-position substitution of glutamic acid with lysine have been reported in association with EDS; however, it is unknown whether this variant would have similar effect (Ghali et al., 2019); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30837697) |
| Division of Medical Genetics at University of Versailles, |
RCV000680211 | SCV000804463 | likely pathogenic | Ehlers-Danlos syndrome, type 4 | no assertion criteria provided | clinical testing | Spontaneous perforation of sigmoid colon started at age 41. |