Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000667100 | SCV000791498 | uncertain significance | Retinitis pigmentosa 25 | 2017-05-17 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000762420 | SCV000892735 | uncertain significance | not provided | 2018-08-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000762420 | SCV001222404 | uncertain significance | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 9 of the EYS gene. It does not directly change the encoded amino acid sequence of the EYS protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs200387978, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has been observed in individual(s) with retinitis pigmentosa (PMID: 23591405). ClinVar contains an entry for this variant (Variation ID: 551928). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Illumina Laboratory Services, |
RCV001162942 | SCV001324931 | uncertain significance | Retinitis pigmentosa | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004768526 | SCV005381336 | uncertain significance | not specified | 2024-08-06 | criteria provided, single submitter | clinical testing | Variant summary: EYS c.1459+5C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0005 in 250482 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in EYS causing Retinitis Pigmentosa (0.0005 vs 0.0034), allowing no conclusion about variant significance. c.1459+5C>T has been reported in the literature in settings of multigene panel testing among individuals affected with Sporadic Retinitis Pigmentosa. These report(s) do not provide unequivocal conclusions about association of the variant with Retinitis Pigmentosa. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23591405, 32531858). ClinVar contains an entry for this variant (Variation ID: 551928). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Department of Clinical Genetics, |
RCV000787832 | SCV000926846 | likely pathogenic | Stargardt disease | 2018-04-01 | no assertion criteria provided | research | |
Natera, |
RCV001162942 | SCV001463562 | uncertain significance | Retinitis pigmentosa | 2020-09-16 | no assertion criteria provided | clinical testing |