ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.1249G>A (p.Gly417Arg)

dbSNP: rs587779637
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000087607 SCV004848340 likely pathogenic Ehlers-Danlos syndrome, type 4 2020-04-16 criteria provided, single submitter clinical testing The p.Gly417Arg variant (previously called p.Gly250Arg) in COL3A1 has been reported in at least 1 individual with clinical features of Ehlers-Danlos syndrome type IV (EDS IV, vascular) (Pepin 2000) and was absent from large population studies. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. Variants in COL3A1 affecting conserved glycine (Gly) residues of the G-X-Y repeat region in the triple helical collagen domain, where this variant is located, are strongly associated with EDS IV (Pepin 2000, Pepin 2014, Frank 2015). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant EDS IV. ACMG/AMP Criteria applied: PM1, PS4_Supporting, PM2, PP3.
Collagen Diagnostic Laboratory, University of Washington RCV000087607 SCV000120497 pathogenic Ehlers-Danlos syndrome, type 4 no assertion criteria provided clinical testing

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