ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.280G>T (p.Ala94Ser)

gnomAD frequency: 0.00001  dbSNP: rs761447734
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
Color Diagnostics, LLC DBA Color Health RCV001192143 SCV001360125 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-10-17 criteria provided, single submitter clinical testing This missense variant replaces alanine with serine at codon 94 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 2/249962 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001876244 SCV002190603 uncertain significance Ehlers-Danlos syndrome, type 4 2022-09-07 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 928328). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. This variant is present in population databases (rs761447734, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 94 of the COL3A1 protein (p.Ala94Ser). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
All of Us Research Program, National Institutes of Health RCV001876244 SCV004830705 uncertain significance Ehlers-Danlos syndrome, type 4 2023-04-27 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant is located in the N-terminal propeptide sequence of the COL3A1 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact 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 has been identified in 2/244760 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively.

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.