ClinVar Miner

Submissions for variant NM_000088.3(COL1A1):c.3452G>T (p.Gly1151Val) (rs72656321)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657897 SCV000779661 pathogenic not provided 2018-05-15 criteria provided, single submitter clinical testing The G1151V missense variant in the COL1A1 gene has been reported previously in association with lethal perinatal osteogenesis imperfecta (Lamande SR et al. 1989). G1151V 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. The G1151V variant is not observed in the gnomAD dataset (Lek et al., 2016). G1151V is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Missense variants in the same (G1151S) and nearby Glycine residues (G1145D and G1154R) 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. Therefore, this pathogenic variant is consistent with a molecular diagnosis of osteogenesis imperfecta.
OMIM RCV000018859 SCV000039142 pathogenic Osteogenesis imperfecta, recessive perinatal lethal 1992-02-01 no assertion criteria provided literature only

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