ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.655G>A (p.Gly219Arg) (rs1131691822)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494511 SCV000582924 pathogenic not provided 2020-01-14 criteria provided, single submitter clinical testing Occurs in the triple helical domain and replaces the glycine in the canonical Gly-X-Y repeat; missense substitution of a canonical glycine residue is expected to disrupt normal protein folding and function, and this is an established mechanism of disease (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31827275)
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV001089571 SCV001244776 pathogenic Stickler syndrome type 1 2018-08-06 criteria provided, single submitter clinical testing A heterozygous missense variant, NM_001844.4(COL2A1):c.655G>A, has been identified in exon 10 of 54 of the COL2A1 gene. The variant is predicted to result in a major amino acid change from glycine to arginine at position 219 of the protein (NP_001835.3(COL2A1):p.(Gly219Arg)). The glycine residue at this position has very high conservation (100 vertebrates, UCSC), and is located within the triple-helical region. In silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD, dbSNP, 1000G). The variant has been previously described as pathogenic in several patients with Stickler syndrome (Hoornaert K. et al. (2010), ClinVar). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.

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