ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.1480G>A (p.Ala494Thr)

gnomAD frequency: 0.00001  dbSNP: rs200866608
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001038875 SCV001202375 uncertain significance Ehlers-Danlos syndrome, type 4 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 494 of the COL3A1 protein (p.Ala494Thr). 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: 837518). 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, LLC DBA Color Health RCV001181186 SCV001346286 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-12-04 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant replaces alanine with threonine at codon 494 of the COL3A1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the 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 is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively.
GeneDx RCV001547709 SCV001767478 uncertain significance not provided 2021-03-17 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 837518; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Occurs in the triple helical domain at the Y 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 Y position is not a common mechanism of disease (Stenson et al., 2014)

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.