Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Blueprint Genetics | RCV001596885 | SCV001832387 | likely pathogenic | not provided | 2019-11-30 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001596885 | SCV004632486 | likely pathogenic | not provided | 2023-06-30 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with autosomal dominant COL2A1-related conditions (PMID: 32071555). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 678 of the COL2A1 protein (p.Gly678Glu). ClinVar contains an entry for this variant (Variation ID: 1224347). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the triple helix domain of COL2A1. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL2A1, variants affecting these glycine residues are significantly enriched in individuals with disease (PMID: 9016532, 17078022) compared to the general population (ExAC). 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 expected to disrupt COL2A1 protein function. |