Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000988820 | SCV001138705 | likely pathogenic | Stickler syndrome type 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003558623 | SCV004295897 | pathogenic | not provided | 2023-06-15 | criteria provided, single submitter | clinical testing | 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). 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) performed at Invitae indicates that this missense variant is expected to disrupt COL2A1 protein function. ClinVar contains an entry for this variant (Variation ID: 802841). This variant is also known as p.Gly805Ser. This missense change has been observed in individual(s) with achondrogenesis type II and/or hypochondrogenesis (PMID: 7741714, 31299979). In at least one individual the variant was observed to be de novo. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1005 of the COL2A1 protein (p.Gly1005Ser). |