ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.1864G>T (p.Gly622Cys)

dbSNP: rs2115921275
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002277777 SCV002564778 likely pathogenic Osteogenesis imperfecta 2020-09-28 criteria provided, single submitter clinical testing
Invitae RCV003774894 SCV004588618 pathogenic Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2022-10-30 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 622 of the COL1A2 protein (p.Gly622Cys). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the triple helix domain of COL1A2. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL1A2, variants affecting these glycine residues are significantly enriched in individuals with disease (PMID: 9016532, 17078022) compared to the general population (ExAC). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C65"). ClinVar contains an entry for this variant (Variation ID: 1701993). This missense change has been observed in individual(s) with osteogenesis imperfecta (Invitae).

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