Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003119288 | SCV003790608 | pathogenic | Ehlers-Danlos syndrome, type 4 | 2020-04-30 | criteria provided, single submitter | clinical testing | This variant is an in-frame deletion of the genomic region encompassing exons 23-24 of the COL3A1 gene. It preserves the integrity of the reading frame. For these reasons, this variant has been classified as Pathogenic. This variant deletes 51 amino acids from the triple helix domain, including p.Gly540. 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 addition, in COL3A1, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 24922459, 25758994) compared to the general population (ExAC). This variant has not been reported in the literature in individuals with COL3A1-related disease. |