Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000181074 | SCV000233350 | uncertain significance | not provided | 2023-03-27 | 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, which includes protein predictors and evolutionary conservation, supports a deleterious effect; 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) |
| Color Diagnostics, |
RCV001176344 | SCV001340308 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-06-21 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with histidine at codon 281 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 cardiovascular disorders in the literature. This variant has not been identified 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. |
| Labcorp Genetics |
RCV001212891 | SCV001384493 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2019-07-24 | 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 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"). This variant has not been reported in the literature in individuals with COL3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 199714). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with histidine at codon 281 of the COL3A1 protein (p.Pro281His). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and histidine. |
| Fulgent Genetics, |
RCV002500525 | SCV002797589 | uncertain significance | Ehlers-Danlos syndrome, type 4; Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome | 2021-08-03 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001176344 | SCV004092536 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-08-08 | criteria provided, single submitter | clinical testing | The p.P281H variant (also known as c.842C>A), located in coding exon 11 of the COL3A1 gene, results from a C to A substitution at nucleotide position 842. The proline at codon 281 is replaced by histidine, an amino acid with similar properties. This amino acid position is well 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. |