Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
All of Us Research Program, |
RCV004805900 | SCV005427370 | likely pathogenic | Ehlers-Danlos syndrome, type 4 | 2024-09-09 | criteria provided, single submitter | clinical testing | The c.3302G>C (p.Gly1101Ala) variant in COL3A1 gene that encodes for collagen type III alpha 1 chain, has not been reported in individuals affected with Ehlers-Danlos syndrome or other COL3A1-related phenotypes. Changes to glycine residues of the COL3A1 protein are significantly enriched in individuals with COL3A1-related conditions (PMID: 24922459, 25758994). Glycine residues within the Gly-X-Y repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In-silico computational prediction tools suggest that the p.Gly1101Ala variant may have deleterious effect on the protein function (REVEL score: 0.937). This variant is absent in the general population database gnomAD (v4.1.0). Other variants at the same amino acid position, p.Gly1101Glu and p.Gly1101Arg, have been interpreted as pathogenic by ClinVar submitters (ClinVar ID: 101126, 17226). Therefore, the c.3302G>C (p.Gly1101Ala) variant in COL3A1 is classified as likely pathogenic. |