ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.203A>G (p.Asp68Gly) (rs376603102)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000771906 SCV000904670 uncertain significance Thoracic aortic aneurysm and aortic dissection 2018-10-24 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant is a missense variant located in the N-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. This variant has been identified in 6/245500 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
GeneDx RCV000709865 SCV000233341 uncertain significance not provided 2018-09-04 criteria provided, single submitter clinical testing p.Asp68Gly (D68G) GAC>GGC: c.203 A>G in exon 2 of the COL3A1 gene (NM_000090.3) The Asp68Gly variant in the COL3A1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The Asp68Gly variant is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. The Asp68 residue is conserved through mammals in evolution. In silico analysis predicts Asp68Gly is probably damaging to the protein structure/function. The Asp68Gly variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Nevertheless, no mutations affecting nearby residues have been reported in association with EDS, indicating this region of the protein may be tolerant of change.With the clinical and molecular information available at this time, we cannot definitively determine if Asp68Gly is a disease-causing mutation or a rare benign variant. The variant is found in TAAD panel(s).
GenomeConnect, ClinGen RCV000709865 SCV000840200 not provided not provided no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Invitae RCV000541054 SCV000631639 uncertain significance Ehlers-Danlos syndrome, type 4 2017-06-12 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 68 of the COL3A1 protein (p.Asp68Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs376603102, ExAC 0.006%). 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: 199708). 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, this variant has uncertain impact on COL3A1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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