Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000524944 | SCV000631675 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 251 of the COL3A1 protein (p.Lys251Arg). This variant is present in population databases (rs151148197, gnomAD 0.002%). 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: 459796). 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 not expected to disrupt COL3A1 protein function with a negative predictive value of 95%. 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. |
| Ambry Genetics | RCV002314961 | SCV000738558 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-07-24 | criteria provided, single submitter | clinical testing | The p.K251R variant (also known as c.752A>G), located in coding exon 10 of the COL3A1 gene, results from an A to G substitution at nucleotide position 752. The lysine at codon 251 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved through mammals, but arginine is the reference amino acid in other 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. |
| Gene |
RCV001764547 | SCV001997927 | uncertain significance | not provided | 2022-09-19 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease (HGMD) |