ClinVar Miner

Submissions for variant NM_001368894.2(PAX6):c.1257_1263del (p.Gln420fs)

dbSNP: rs1554982299
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000541782 SCV000632658 pathogenic Aniridia 1; Irido-corneo-trabecular dysgenesis 2017-07-19 criteria provided, single submitter clinical testing This sequence change deletes 7 nucleotides from the PAX6 mRNA resulting in a frameshift p.Gln406Profs*117). This is not anticipated to result in nonsense mediated decay but it is expected to disrupt the last 18 amino acids of the PAX6 protein and extend it by an additional 100 amino acids. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PAX6-related disease.  However similar C-terminal extensions (p.Pro419Glnfs*106 and p.Asp413Glufs*112) have been reported in individuals affected with aniridia (PMID: 26661695, 12731001). For these reasons, this variant has been classified as Pathogenic. An amino acid that is disrupted by this frameshift variant, p.Gln422, has been shown to be functionally important. Experimental studies have shown that an amino acid substitution at codon 422 (p.Gln422Arg) disrupts the DNA and protein binding ability of the PAX6 protein (PMID:11309364, 16098226).

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