Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002314222 | SCV000738553 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-06-06 | criteria provided, single submitter | clinical testing | The p.P223A variant (also known as c.667C>G), located in coding exon 8 of the COL3A1 gene, results from a C to G substitution at nucleotide position 667. The proline at codon 223 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001229407 | SCV001401852 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2019-09-02 | criteria provided, single submitter | clinical testing | 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 C0"). 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. This variant has not been reported in the literature in individuals with COL3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 519614). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 223 of the COL3A1 protein (p.Pro223Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. |