ClinVar Miner

Submissions for variant NM_001142800.2(EYS):c.4120C>T (p.Arg1374Ter)

gnomAD frequency: 0.00003  dbSNP: rs928803207
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000987728 SCV001137163 pathogenic Retinitis pigmentosa 25 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001062996 SCV001227824 pathogenic not provided 2024-10-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1374*) in the EYS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EYS are known to be pathogenic (PMID: 18836446, 20333770). This variant is present in population databases (no rsID available, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with retinitis pigmentosa (PMID: 21069908, 29159838, 29550188). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 802236). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003226411 SCV003922790 pathogenic Retinitis pigmentosa 2023-03-21 criteria provided, single submitter clinical testing Variant summary: EYS c.4120C>T (p.Arg1374X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.3e-05 in 153766 control chromosomes (gnomAD). c.4120C>T has been reported in the literature as a biallelic genotype in individuals affected with Retinitis Pigmentosa (e.g. Barragan_2010, Sengillo_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variant since 2014: all three classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel RCV003226411 SCV004030402 pathogenic Retinitis pigmentosa 2023-07-24 criteria provided, single submitter research Clinical significance based on ACMG v2.0
Baylor Genetics RCV000987728 SCV004192929 pathogenic Retinitis pigmentosa 25 2024-03-20 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000987728 SCV005670609 pathogenic Retinitis pigmentosa 25 2024-05-17 criteria provided, single submitter clinical testing
Natera, Inc. RCV001274881 SCV001459423 pathogenic Autosomal recessive retinitis pigmentosa 2020-09-16 no assertion criteria provided clinical testing

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