ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.3626G>C (p.Gly1209Ala) (rs374452484)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center RCV000210901 SCV000264599 likely benign Ehlers-Danlos syndrome, type 4 2015-12-01 criteria provided, single submitter research
Color RCV000772065 SCV000905094 uncertain significance Thoracic aortic aneurysm and aortic dissection 2018-10-09 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located near the C-terminal propeptide of the COL3A1 protein, in a region that is not highly conserved. 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 has been identified in 6/246158 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Invitae RCV000210901 SCV000541798 uncertain significance Ehlers-Danlos syndrome, type 4 2018-08-13 criteria provided, single submitter clinical testing This sequence change replaces glycine with alanine at codon 1209 of the COL3A1 protein (p.Gly1209Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. This variant is present in population databases (rs374452484, ExAC 0.004%) but has not been reported in the literature in individuals with a COL3A1-related disease. ClinVar contains an entry for this variant (Variation ID: 225283). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but 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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