Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001184519 | SCV001350501 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-06-05 | criteria provided, single submitter | clinical testing | This variant causes an in-frame deletion of glycine at codon 168 of the COL3A1 protein. This variant affects one of the conserved glycine residues within the Gly-Xaa-Yaa repeat motifs of the triple helical domain of the COL3A1 protein that are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). To our knowledge, this variant has not been reported in individuals affected with COL3A1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion for a pathogenic role, the available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV001876139 | SCV002316552 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2022-03-18 | criteria provided, single submitter | clinical testing | This variant, c.502_504del, results in the deletion of 1 amino acid(s) of the COL3A1 protein (p.Gly168del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 923647). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV003225154 | SCV003921671 | likely pathogenic | not provided | 2022-10-30 | criteria provided, single submitter | clinical testing | In-frame deletion of 1 amino acid in a non-repeat region; Occurs in the triple helical domain and is predicted to remove canonical Gly-X-Y repeat units; an in-frame deletion variant in this region is expected to disrupt normal protein folding and function, and this is an established mechanism of disease (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |