ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.395G>A (p.Arg132His)

gnomAD frequency: 0.00009  dbSNP: rs372678526
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000659369 SCV000781180 uncertain significance Connective tissue disorder 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV002235525 SCV001505853 uncertain significance Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2024-01-02 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 132 of the COL1A2 protein (p.Arg132His). This variant is present in population databases (rs372678526, gnomAD 0.02%). This missense change has been observed in individual(s) with osteogenesis imperfecta (PMID: 31363794). ClinVar contains an entry for this variant (Variation ID: 547235). 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001507698 SCV001713400 uncertain significance not provided 2020-08-26 criteria provided, single submitter clinical testing
GeneDx RCV001507698 SCV001756460 uncertain significance not provided 2022-10-18 criteria provided, single submitter clinical testing Has been reported in association with osteogenesis imperfecta (Ohata et al., 2019); however, specific clinical information was not provided; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat. Although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease (HGMD); This variant is associated with the following publications: (PMID: 31363794)

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