Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV003341828 | SCV004051327 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-07-24 | criteria provided, single submitter | clinical testing | The p.T623A variant (also known as c.1867A>G), located in coding exon 26 of the COL3A1 gene, results from an A to G substitution at nucleotide position 1867. The threonine at codon 623 is replaced by alanine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
All of Us Research Program, |
RCV004011271 | SCV004836190 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 623 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 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. |