ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.3413C>T (p.Pro1138Leu) (rs201880122)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000772083 SCV000905115 uncertain significance Thoracic aortic aneurysm and aortic dissection 2018-07-23 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the triple-helical region of the COL3A1 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact the 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 52/277164 chromosomes (47/126666 non-Finnish European chromosomes) in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Invitae RCV000473742 SCV000541812 uncertain significance Ehlers-Danlos syndrome, type 4 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1138 of the COL3A1 protein (p.Pro1138Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs201880122, ExAC 0.03%). This variant has not been reported in the literature in individuals with a COL3A1-related disease ClinVar contains an entry for this variant (Variation ID: 404306). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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