ClinVar Miner

Submissions for variant NM_000088.3(COL1A1):c.2944C>A (p.Pro982Thr) (rs141117382)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000429625 SCV000530662 uncertain significance not provided 2018-08-09 criteria provided, single submitter clinical testing The P982T variant in the COL1A1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P982T variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P982T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, affecting the Y residue of the triple-helical region containing Gly-X-Y repeats. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P982T as a variant of uncertain significance.
Invitae RCV000631461 SCV000752541 uncertain significance Osteogenesis imperfecta type I 2018-08-02 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 982 of the COL1A1 protein (p.Pro982Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs141117382, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with COL1A1-related disease. ClinVar contains an entry for this variant (Variation ID: 388368). 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.

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