Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001948759 | SCV002213777 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2022-10-08 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with Ehlers-Danlos syndrome, classical type (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 1671 of the COL5A1 protein (p.Cys1671Phe). ClinVar contains an entry for this variant (Variation ID: 1437556). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL5A1 protein function. |
| Ambry Genetics | RCV004612023 | SCV005106053 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-04-25 | criteria provided, single submitter | clinical testing | The p.C1671F variant (also known as c.5012G>T), located in coding exon 63 of the COL5A1 gene, results from a G to T substitution at nucleotide position 5012. The cysteine at codon 1671 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |