Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001190254 | SCV000738549 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-03-25 | criteria provided, single submitter | clinical testing | The p.A1389S variant (also known as c.4165G>T), located in coding exon 50 of the COL3A1 gene, results from a G to T substitution at nucleotide position 4165. The alanine at codon 1389 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV000803251 | SCV000943113 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2023-04-22 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 519613). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. This variant is present in population databases (rs202022204, gnomAD 0.004%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1389 of the COL3A1 protein (p.Ala1389Ser). |
Color Diagnostics, |
RCV001190254 | SCV001357705 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-03-15 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with serine at codon 1389 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). 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 3/282702 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, |
RCV000803251 | SCV004828187 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with serine at codon 1389 of the COL3A1 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <=0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/282702 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. |