Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000703207 | SCV000832096 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 401 of the COL3A1 protein (p.Ala401Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs373858715, ExAC 0.01%). 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. |
Color Diagnostics, |
RCV001524996 | SCV001734982 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-01-05 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 401 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 cardiovascular disorders in the literature. This variant has been identified in 2/251172 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. |
Ambry Genetics | RCV001524996 | SCV004051333 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-08-03 | criteria provided, single submitter | clinical testing | The p.A401T variant (also known as c.1201G>A), located in coding exon 18 of the COL3A1 gene, results from a G to A substitution at nucleotide position 1201. The alanine at codon 401 is replaced by threonine, an amino acid with similar properties. This variant co-occurred with an MYH11 variant in an individual with initial differential diagnosis of thoracic aortic aneurysm and dissection and possible vascular Ehlers-Danlos syndrome; however, clinical details were not provided (Renner S et al. Genet Med, 2019 Aug;21:1832-1841). This amino acid position is not 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. |