ClinVar Miner

Submissions for variant NM_001142800.2(EYS):c.4613_4616del (p.Leu1538fs)

dbSNP: rs1582929649
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001002386 SCV001160304 pathogenic Retinitis pigmentosa 25 2019-03-04 criteria provided, single submitter clinical testing The EYS c.4613_4616delTCAC; p.Leu1538fs variant, to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is also absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting four nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, EYS loss-of-function is an established mechanism of disease and numerous truncating variants downstream of p.Leu1538fs have been reported in individuals with retinitis pigmentosa and are considered pathogenic (Arai 2015, Audo 2010). Based on available information, this variant is considered to be pathogenic. References: Arai Y et al. Retinitis Pigmentosa with EYS Mutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations. J Ophthalmol. 2015;2015:819760. Audo I et al. EYS is a major gene for rod-cone dystrophies in France. Hum Mutat. 2010 May;31(5):E1406-35.
Labcorp Genetics (formerly Invitae), Labcorp RCV002549178 SCV003312612 pathogenic not provided 2022-09-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 811908). This variant has not been reported in the literature in individuals affected with EYS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu1538Glnfs*11) 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).

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