ClinVar Miner

Submissions for variant NM_000095.3(COMP):c.925G>A (p.Gly309Arg)

dbSNP: rs2145903203
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India RCV001806405 SCV002053976 pathogenic Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome criteria provided, single submitter clinical testing
Invitae RCV003560854 SCV004297282 pathogenic not provided 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 309 of the COMP protein (p.Gly309Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with pseudoachondroplasia (PMID: 9756911, 34709441, 34750995). ClinVar contains an entry for this variant (Variation ID: 1332831). 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 expected to disrupt COMP protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects COMP function (PMID: 17570134). For these reasons, this variant has been classified as Pathogenic.

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