ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.2717G>A (p.Arg906His)

gnomAD frequency: 0.00010  dbSNP: rs147063981
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002232467 SCV000627319 uncertain significance Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2023-12-07 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 906 of the COL1A2 protein (p.Arg906His). This variant is present in population databases (rs147063981, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with osteogenesis imperfecta (PMID: 25289482). ClinVar contains an entry for this variant (Variation ID: 487454). 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) performed at Invitae indicates that this missense variant is expected to disrupt COL1A2 protein function with a positive predictive value of 95%. 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.
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000791074 SCV000930344 uncertain significance not specified 2019-04-27 criteria provided, single submitter clinical testing
GeneDx RCV001580519 SCV001817536 uncertain significance not provided 2020-09-28 criteria provided, single submitter clinical testing Has been reported as a variant of uncertain significance in a child with OI type IV (Lindahl et a., 2015), and in a fetus with OI type III (Wu et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; 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 (Stenson et al., 2014); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 487454; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 25289482, 25944380)

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