Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001387003 | SCV001587474 | pathogenic | not provided | 2020-10-14 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the EYS gene (p.Arg3094Valfs*4). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 51 amino acid(s) of the EYS protein. For these reasons, this variant has been classified as Pathogenic. 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. This variant has been observed in individual(s) with retinitis pigmentosa (PMID: 22581970). ClinVar contains an entry for this variant (Variation ID: 224759). This variant is not present in population databases (ExAC no frequency). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003114370 | SCV003800865 | likely pathogenic | Retinitis pigmentosa | 2023-01-31 | criteria provided, single submitter | clinical testing | Variant summary: EYS c.9277_9278dupGG (p.Arg3094ValfsX4) is located in exon 43 (i.e. in the last exon), and results in a premature termination codon that is not expected to cause nonsense mediated decay (NMD), but is predicted to cause a truncation of the encoded protein, that removes a part of the fifth laminin G domain (amino acids 2975-3165; IPR001791). Truncations downstream of this position have been reported in affected individuals (HGMD). The variant was absent in 155724 control chromosomes (gnomAD). c.9277_9278dupGG has been reported in the literature in at least one compound heterozygous individual affected with inherited retinal disease (O'Sullivan_2012, Ellingford_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Centre for Genomic Medicine, |
RCV000210301 | SCV000259108 | likely pathogenic | Retinal dystrophy | 2015-01-30 | no assertion criteria provided | clinical testing | |
Natera, |
RCV001828049 | SCV002083454 | pathogenic | Retinitis pigmentosa 25 | 2020-12-07 | no assertion criteria provided | clinical testing |