ClinVar Miner

Submissions for variant NM_001142800.2(EYS):c.6416G>A (p.Cys2139Tyr) (rs749909863)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000169660 SCV000221188 uncertain significance not specified 2014-07-15 criteria provided, single submitter clinical testing The Cys2139Tyr variant in EYS has been reported in 3 compound heterozygous and 1 heterozygous individuals with retinitis pigmentosa and was found to segregate with disease in 3 compound heterozygous family members (Audo 2010, Abd El-Aziz 2010, Jin 2014). This variant was not identified in large population studies. Computational analyses (biochemical amino acid properties, conservation, PolyPhen2, and SIFT) don't provide strong support for or against and impact to the protein and one mammal carries a tyrosine (Tyr) at this position. In summary, while segregation studies and the presence of this variant in combination with other reported pathogenic variants indicate this variant may be disease-causing, the presence of the variant amino acid in a mammal raises some concern and additional studies are required to fully establish its clinical significance.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000177524 SCV000229407 pathogenic not provided 2016-12-29 criteria provided, single submitter clinical testing
Invitae RCV000177524 SCV000948230 pathogenic not provided 2020-10-14 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 2139 of the EYS protein (p.Cys2139Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is present in population databases (rs749909863, ExAC 0.2%). This variant has been observed to segregate with retinitis pigmentosa in a family (PMID: 25753737). This variant has also been observed in many unrelated individuals affected with retinitis pigmentosa (PMID: 20333770, 25753737, 25356976). ClinVar contains an entry for this variant (Variation ID: 189230). 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. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075403 SCV001241025 pathogenic Retinal dystrophy 2018-07-19 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000177524 SCV001248822 pathogenic not provided 2019-05-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000177524 SCV001446977 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001376308 SCV001573403 likely pathogenic Retinitis pigmentosa 25 2021-04-08 criteria provided, single submitter research The EYS c.6416G>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PS1, PM2, PP1, PP3. Based on this evidence we have classified this variant as Likely Pathogenic.

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