Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000199292 | SCV000249986 | uncertain significance | not provided | 2014-02-16 | criteria provided, single submitter | clinical testing | p.Gly1309Asp (G1309D) GGT>GAT: c.3926 G>A in exon 52 of the COL5A2 gene (NM_000393.3). The G1309D variant in the COL5A2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. G1309D was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. G1309D is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. The G1309 residue is highly conserved across species and in silico analysis predicts G1309D is damaging to the protein structure/function. However, mutations in nearby residues have not been reported, indicating this region of the protein may tolerate change. With the clinical and molecular information available at this time, we cannot definitively determine if G1309D in the COL5A2 gene is a disease-causing mutation or a rare benign variant. This variant was found in COL5A2,TAAD. |
| Invitae | RCV002229095 | SCV001236024 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2021-06-16 | criteria provided, single submitter | clinical testing | 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. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C65"). This variant has not been reported in the literature in individuals with COL5A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 213123). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 1309 of the COL5A2 protein (p.Gly1309Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. |