Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001002455 | SCV001160397 | uncertain significance | not specified | 2019-03-28 | criteria provided, single submitter | clinical testing | The COL3A1 c.946G>T; p.Ala316Ser variant (rs958176385), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is also absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The alanine at codon 316 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, due to limited information, the clinical significance of the p.Ala316Ser variant is uncertain at this time. |
Labcorp Genetics |
RCV001042766 | SCV001206468 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2024-01-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 316 of the COL3A1 protein (p.Ala316Ser). This variant is not present in population databases (gnomAD no frequency). 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: 811944). 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. |
Color Diagnostics, |
RCV001191595 | SCV001359468 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-11-29 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with serine at codon 316 of the COL3A1 protein. Computational prediction tool indicates that this variant may have a neutral impact on protein structure and function. 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 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. |
Gene |
RCV003106092 | SCV003761903 | uncertain significance | not provided | 2023-01-30 | 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); Occurs in the triple helical domain at the X 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 X position is not a common mechanism of disease (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function |
All of Us Research Program, |
RCV001042766 | SCV004833601 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2024-05-14 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with serine at codon 316 of the COL3A1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant 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). 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 | RCV001191595 | SCV005103889 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-04-28 | criteria provided, single submitter | clinical testing | The p.A316S variant (also known as c.946G>T), located in coding exon 13 of the COL3A1 gene, results from a G to T substitution at nucleotide position 946. The alanine at codon 316 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |