Submissions for variant NM_001142800.2(EYS):c.586A>C (p.Lys196Gln)

gnomAD frequency: 0.00005  dbSNP: rs749038401

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000943591	SCV001089543	likely benign	not provided	2024-12-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002222648	SCV002500084	uncertain significance	not specified	2022-03-04	criteria provided, single submitter	clinical testing	Variant summary: EYS c.586A>C (p.Lys196Gln) results in a conservative amino acid change located in the EGF-like domain (IPR000742) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 251166 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in EYS causing Retinitis Pigmentosa (0.00018 vs 0.0034), allowing no conclusion about variant significance. Although reported in the literature, to our knowledge, no penetrant association of c.586A>C in individuals affected with Retinitis Pigmentosa and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Dept Of Ophthalmology, Nagoya University	RCV003890098	SCV004704673	uncertain significance	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV003890098	SCV005071200	uncertain significance	Retinal dystrophy	2019-01-01	criteria provided, single submitter	clinical testing