ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.2222G>A (p.Gly741Asp)

dbSNP: rs553203474
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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 RCV000087343 SCV004847685 likely pathogenic Ehlers-Danlos syndrome, type 4 2019-04-17 criteria provided, single submitter clinical testing The p.Gly741Asp variant in COL3A1 has been identified in 2 individuals with vascular Ehlers Danlos syndrome (vEDS; Frank 2015, Pepin 2014) and was absent from large population studies. In addition, 2 other variants at the same position (p.Gly741Cys and p.Gly741Ser) have also been identified in individuals with vEDS (Inokuchi 2014, Frank 2015, Pepin 2014, ClinVar), suggesting changes at this position are not tolerated. Computational prediction tools and conservation analysis suggest that the p.Gly741Asp variant may impact the protein, though this information is not predictive enough to determine pathogenicity. Furthermore, this variant affects a highly conserved glycine (Gly) residue in the Gly-X-Y motif, which is a common finding in individuals with vEDS. 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 vascular Ehlers Danlos syndrome. ACMG/AMP Criteria applied: PM1; PM2; PM5; PP3; PS4_Supporting.
Collagen Diagnostic Laboratory, University of Washington RCV000087343 SCV000120223 pathogenic Ehlers-Danlos syndrome, type 4 no assertion criteria provided clinical testing

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