ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.3691A>G (p.Thr1231Ala)

gnomAD frequency: 0.00005  dbSNP: rs201560619
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000434912 SCV000536545 uncertain significance not provided 2023-04-11 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not located in the triple helical region, where the majority of pathogenic missense variants occur (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function
Invitae RCV001851102 SCV002276963 uncertain significance Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2023-10-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1231 of the COL1A2 protein (p.Thr1231Ala). This variant is present in population databases (rs201560619, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 393173). 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. 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.
Ambry Genetics RCV004022528 SCV005032285 uncertain significance Cardiovascular phenotype 2024-02-24 criteria provided, single submitter clinical testing The p.T1231A variant (also known as c.3691A>G), located in coding exon 50 of the COL1A2 gene, results from an A to G substitution at nucleotide position 3691. The threonine at codon 1231 is replaced by alanine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.

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