Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002241211 | SCV001386484 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1164 of the COL1A2 protein (p.Arg1164His). This variant is present in population databases (rs764327381, gnomAD 0.007%). This missense change has been observed in individual(s) with osteogenesis imperfecta, type IV (PMID: 27509835). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 944390). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL1A2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV001760190 | SCV001988974 | uncertain significance | not provided | 2019-03-04 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in 1/15292 (0.0065%) alleles from individuals of African ancestry in large population cohorts (Lek et al., 2016).; Missense variants in nearby residues (C1163R, D1165E) have been reported in the Human Gene Mutation Database in association with osteogenesis imperfecta (Stenson et al., 2014).; Has been reported in a single family in association with osteogenesis imperfecta (Bardai et al., 2016); This variant is associated with the following publications: (PMID: 27509835) |