ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.2606C>A (p.Pro869His) (rs794728052)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181098 SCV000233374 uncertain significance not provided 2013-04-08 criteria provided, single submitter clinical testing p.Pro869His (CCT>CAT): c.2606 C>A in exon 37 of the COL3A1 gene (NM_000090.3) The Pro869His variant in the COL3A1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Although Pro869His results in a non-conservative amino acid substitution of a non-polar Proline residue with a positively charged Histidine residue, the Pro869 position is not conserved across species. However, mutations affecting nearby residues (Gly852Cys, Gly879Val) have been reported in association with EDS, supporting the functional importance of this region of the protein. Furthermore, the Pro869His variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. With the clinical and molecular information available at this time, we cannot definitively determine if Pro869His is a disease-causing mutation or a rare benign variant. The variant is found in TAAD panel(s).
Invitae RCV000230019 SCV000283462 uncertain significance Ehlers-Danlos syndrome, type 4 2016-03-27 criteria provided, single submitter clinical testing This sequence change replaces proline with histidine at codon 869 of the COL3A1 protein (p.Pro869His). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and histidine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a COL3A1-related disease. ClinVar contains an entry for this variant (Variation ID: 199732). 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 is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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