ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.3655G>T (p.Asp1219Tyr) (rs760093841)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000429122 SCV000535568 likely pathogenic not provided 2017-01-05 criteria provided, single submitter clinical testing The D1219Y variant in the COL2A1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D1219Y variant was not observed 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 D1219Y 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. A missense variant in the same residue (D1219H) has been reported in association with spondyloepimetaphyseal dysplasia, supporting the functional importance of this residue (Hammarsjo et al., 2016). In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, the D1219Y variant is a strong candidate for a pathogenic variant; however the possibility it may be a rare benign variant cannot be completely excluded.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000429122 SCV001250093 uncertain significance not provided 2020-03-01 criteria provided, single submitter clinical testing

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