ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.1727A>G (p.His576Arg)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002399135 SCV002713700 uncertain significance Cardiovascular phenotype 2022-10-25 criteria provided, single submitter clinical testing The p.H576R variant (also known as c.1727A>G), located in coding exon 30 of the COL1A2 gene, results from an A to G substitution at nucleotide position 1727. The histidine at codon 576 is replaced by arginine, an amino acid with highly similar properties. This alteration has been reported in an osteogenesis imperfecta cohort (Lindahl K et al. Eur J Hum Genet, 2015 Aug;23:1042-50). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV003100806 SCV003261424 uncertain significance Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2022-12-30 criteria provided, single submitter clinical testing 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. 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 not expected to disrupt COL1A2 protein function. ClinVar contains an entry for this variant (Variation ID: 1778877). This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. This variant is present in population databases (rs368676099, gnomAD 0.003%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 576 of the COL1A2 protein (p.His576Arg).

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