Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000774279 | SCV000907981 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-09-20 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with threonine at codon 1407 of the COL3A1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with COL3A1-related disorders in the literature. This variant has been identified in 6/282792 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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. |
| Ambry Genetics | RCV000774279 | SCV002630746 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-07-19 | criteria provided, single submitter | clinical testing | The p.K1407T variant (also known as c.4220A>C), located in coding exon 50 of the COL3A1 gene, results from an A to C substitution at nucleotide position 4220. The lysine at codon 1407 is replaced by threonine, an amino acid with similar properties, and is located in the C-terminal propeptide. This amino acid position is highly conserved through mammals but not in all 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 |
RCV002534129 | SCV003474899 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2022-08-21 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 1407 of the COL3A1 protein (p.Lys1407Thr). This variant is present in population databases (rs747651283, gnomAD 0.005%). 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: 629570). 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. 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. |
| All of Us Research Program, |
RCV002534129 | SCV004828198 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2024-05-14 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with threonine at codon 1407 of the COL3A1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with COL3A1-related disorders in the literature. This variant has been identified in 6/282792 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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. |