Submissions for variant NM_001368894.2(PAX6):c.760C>T (p.Arg254Ter)

dbSNP: rs121907917

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000312176	SCV000329450	pathogenic	not provided	2022-05-26	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26350204, 27381094, 27231702, 27081561, 27455012, 22692063, 12634864, 25525159, 7550230, 9482572, 19876904, 16803629, 1345175, 26849621, 27081502, 10887930, 21423868, 29901133, 19862335, 21850189, 23761016, 30221735, 32360764, 15740668, 33169869, 33494148, 34101622, 32467297)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000536976	SCV000632669	pathogenic	Aniridia 1; Irido-corneo-trabecular dysgenesis	2023-10-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg240*) in the PAX6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAX6 are known to be pathogenic (PMID: 12634864). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with aniridia (PMID: 19862335, 21423868, 21850189, 22692063, 23761016, 26849621, 27081502, 27455012). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 3467). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Wessex Regional Genetics Laboratory, Salisbury District Hospital	RCV000003632	SCV001055787	pathogenic	Aniridia 1	2019-08-15	criteria provided, single submitter	clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital	RCV000312176	SCV001449755	pathogenic	not provided	2014-05-28	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000312176	SCV001905670	pathogenic	not provided	2021-09-15	criteria provided, single submitter	clinical testing
OMIM	RCV000003632	SCV000023795	pathogenic	Aniridia 1	2009-11-01	no assertion criteria provided	literature only
Laboratory of Genetic Epidemiology, Research Centre for Medical Genetics	RCV000003632	SCV000584155	pathogenic	Aniridia 1		no assertion criteria provided	research