ClinVar Miner

Submissions for variant NM_000280.4(PAX6):c.622C>T (p.Arg208Trp) (rs757259413)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413794 SCV000490693 likely pathogenic not provided 2019-09-09 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 9147640, 12015275, 29450879, 7550230, 8364574, 9482572, 10234503, 22361317, 29930474, 10737978, 32360764)
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000413794 SCV000708115 likely pathogenic not provided 2017-05-08 criteria provided, single submitter clinical testing
Invitae RCV001388984 SCV001590181 pathogenic Aniridia 1; Irido-corneo-trabecular dysgenesis 2020-05-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 208 of the PAX6 protein (p.Arg208Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs757259413, ExAC 0.001%). This variant has been observed in individual(s) with aniridia or congenital cataracts (PMID: 8364574, 22361317). ClinVar contains an entry for this variant (Variation ID: 372441). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 372441). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg208 amino acid residue in PAX6. Other variant(s) that disrupt this residue have been observed in individuals with PAX6-related conditions (PMID: 10234503), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Wessex Regional Genetics Laboratory,Salisbury District Hospital RCV000984424 SCV001055779 likely pathogenic Aniridia 1 2019-08-15 no assertion criteria provided clinical testing
Institute of Human Genetics, Klinikum rechts der Isar RCV000984424 SCV001430017 pathogenic Aniridia 1 2020-07-21 no assertion criteria provided clinical testing

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