Submissions for variant NM_001368894.2(PAX6):c.76C>T (p.Arg26Trp)

dbSNP: rs121907913

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002550582	SCV003440286	pathogenic	Aniridia 1; Irido-corneo-trabecular dysgenesis	2024-09-06	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 26 of the PAX6 protein (p.Arg26Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of aniridia (PMID: 27878435, 32360764). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 800389). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PAX6 protein function with a positive predictive value of 80%. This variant disrupts the p.Arg26 amino acid residue in PAX6. Other variant(s) that disrupt this residue have been observed in individuals with PAX6-related conditions (PMID: 18483559, 31700164, 34101622), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Molecular Medicine, University of Pavia	RCV003489985	SCV004022323	pathogenic	Irido-corneo-trabecular dysgenesis	2023-07-28	criteria provided, single submitter	research
Wessex Regional Genetics Laboratory, Salisbury District Hospital	RCV000984359	SCV001055707	likely pathogenic	Aniridia 1	2019-08-15	no assertion criteria provided	clinical testing