ClinVar Miner

Submissions for variant NM_001142800.2(EYS):c.8243dup (p.Leu2748fs) (rs1240944758)

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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 RCV000757242 SCV000885391 likely pathogenic not provided 2018-05-15 criteria provided, single submitter clinical testing The EYS c.8243dupT; p.Leu2748fs variant, to our knowledge, is not reported in the medical literature or gene-specific databases. However, other insertions and deletions in this region are described in the medical literature in individuals with retinitis pigmentosa (Huang 2015, McGuigan 2017). The c.8243dupT variant is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant results in a premature termination codon in the last exon of the EYS gene more than 300 amino acids from the wild-type termination codon, and is thus predicted to result in mRNA subject to nonsense-mediated decay or a truncated protein. Considering available information, this variant is classified as likely pathogenic. Pathogenic EYS variants are causative for autosomal recessive retinitis pigmentosa (MIM: 602772). References: Huang XF et al. Genotype-phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing. Genet Med. 2015 Apr;17(4):271-8. McGuigan DB EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression. Genes (Basel). 2017 Jul 12;8(7). pii: E178.
Invitae RCV000757242 SCV001591318 pathogenic not provided 2020-09-10 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the EYS gene (p.Leu2748Phefs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 397 amino acids of the EYS protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with retinitis pigmentosa (PMID: 25356976). It is also known as c.8244_8245insT in the literature. ClinVar contains an entry for this variant (Variation ID: 618633). This variant disrupts the C-terminus of the EYS protein. Other variant(s) that disrupt this region (p.Tyr3135*) have been determined to be pathogenic (PMID: 18976725, 31074760, 29159838, 30337596). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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