ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.2059G>A (p.Gly687Ser)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV001270004 SCV001450418 likely pathogenic not provided 2019-01-08 criteria provided, single submitter clinical testing
Baylor Genetics RCV001332046 SCV001524244 likely pathogenic Czech dysplasia, metatarsal type 2019-12-17 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV001270004 SCV001591751 pathogenic not provided 2020-10-29 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 687 of the COL2A1 protein (p.Gly687Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with autosomal dominant COL2A1-related conditions (PMID: 22791362, 25967556, 26626311). It has also been observed to segregate with disease in related individuals. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL2A1, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 10612821, 26443184) compared to the general population (ExAC). This variant disrupts the p.Gly687 amino acid residue in COL2A1. Other variant(s) that disrupt this residue have been observed in individuals with COL2A1-related conditions (PMID: 22791362, 26626311), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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