ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.3796A>C (p.Lys1266Gln)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000772997 SCV000906379 uncertain significance Thoracic aortic aneurysm and aortic dissection 2018-06-04 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant is a missense variant located in the C-terminal propeptide domain 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 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 is rare in the general population and has been identified has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Invitae RCV000689285 SCV000816927 uncertain significance Ehlers-Danlos syndrome, type 4 2018-04-03 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 1266 of the COL3A1 protein (p.Lys1266Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual undergoing clinical genetic testing for concern of a connective tissue disorder (PMID: 25834947). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably damaging"; 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.

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