Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001058086 | SCV001222629 | pathogenic | Ehlers-Danlos syndrome, type 4 | 2019-11-26 | criteria provided, single submitter | clinical testing | 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 COL3A1, variants that affect these glycine residues are significantly enriched in individuals with disease (PMID: 24922459, 25758994) compared to the general population (ExAC). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly978 amino acid residue in COL3A1. Other variant(s) that disrupt this residue have been observed in individuals with COL3A1-related conditions (PMID: 16863833, 29216800, 24922459, 27611364), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with COL3A1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 978 of the COL3A1 protein (p.Gly978Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. |