Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000555113 | SCV000631620 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2021-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 400 of the COL3A1 protein (p.Pro400Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. 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. |
Ambry Genetics | RCV000772105 | SCV000738546 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-02-14 | criteria provided, single submitter | clinical testing | The p.P400S variant (also known as c.1198C>T), located in coding exon 18 of the COL3A1 gene, results from a C to T substitution at nucleotide position 1198. The proline at codon 400 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and serine 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. |
Color Diagnostics, |
RCV000772105 | SCV000905141 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-03-11 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 400 of the COL3A1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 been identified in 1/251182 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. |
All of Us Research Program, |
RCV000555113 | SCV004826930 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2023-05-31 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 400 of the COL3A1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 been identified in 1/251182 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. |