ClinVar Miner

Submissions for variant NM_000280.4(PAX6):c.52G>C (p.Gly18Arg) (rs886044289)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000317485 SCV000344276 likely pathogenic not provided 2016-08-02 criteria provided, single submitter clinical testing
Invitae RCV000635404 SCV000756817 pathogenic Aniridia 1; Irido-corneo-trabecular dysgenesis 2018-03-20 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 18 of the PAX6 protein (p.Gly18Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with PAX6-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 289849). Experimental studies have shown that this missense change results in a PAX6 protein with reduced transcriptional activation capabilities (PMID: 15579687, 20577777). A different variant (c.52G>A) giving rise to the same protein effect observed here (p.Gly18Arg) has been reported in an individual affected with Peter's anomaly (PMID: 16712695). In addition, a different missense substitution at this codon (p.Gly18Trp) has also been reported in an individual affected with Peter's anomaly (PMID: 9792406). These observations suggest that this residue may be critical for protein function. For these reasons, this variant has been classified as Pathogenic.

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