ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.3319G>A (p.Gly1107Arg) (rs587779561)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Collagen Diagnostic Laboratory,University of Washington RCV000087504 SCV000120391 pathogenic Ehlers-Danlos syndrome, type 4 no assertion criteria provided clinical testing
Invitae RCV000087504 SCV000283465 likely pathogenic Ehlers-Danlos syndrome, type 4 2016-02-24 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1107 of the COL3A1 protein (p.Gly1107Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in two patients affected with vascular Ehlers-Danlos syndrome (PMID: 24922459, 24650746). ClinVar contains an entry for this variant (Variation ID: 101267). 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"). Glycine residues within the triple helix region are crucial to maintain fibrillar collagens structure and stability (PMID: 7695699, 19344236). In the case of COL3A1, the majority of missense substitutions within the triplex helix domain affect glycine residues in patients with vascular Ehlers-Danlos syndrome (PMID: 24922459, 25758994). In summary, this variant is a rare missense change that has been reported in two affected patients and it affects one of the glycine residues within the triple helix of the COL3A1 protein, which are thought to be damaging . For these reasons, it has been classified as Likely Pathogenic.

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