ClinVar Miner

Submissions for variant NM_000088.3(COL1A1):c.1247G>A (p.Gly416Asp) (rs1135401953)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues RCV000496233 SCV000588153 pathogenic Osteogenesis imperfecta type I 2017-03-30 criteria provided, single submitter clinical testing
GeneDx RCV000520103 SCV000621867 pathogenic not provided 2017-10-20 criteria provided, single submitter clinical testing The G416D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. G416D occurs in the triple helical domain and replaces the Glycine in the canonical Gly-X-Y repeat. Variants in these Glycines result in poor winding of the collagen triple helix and a less functional protein. G416D is not observed in large population cohorts (Lek et al., 2016). The G416D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby Glycine residues (G413A, P417A, G422C) have been reported in the Human Gene Mutation Database in association with osteogenesis imperfecta (Stenson et al., 2014), supporting the functional importance of this region of the protein.

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