Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000778922 | SCV000915337 | uncertain significance | Retinitis pigmentosa | 2017-04-27 | criteria provided, single submitter | clinical testing | The EYS c.7394C>G (p.Thr2465Ser) variant has been reported in at least two studies in which it is found in a compound heterozygous state with a stop-gained variant in one patient and in eight additional patient alleles with unknown zygosity, all of whom are affected with retinitis pigmentosa (Hosono et al. 2012; Yoon et al. 2015). The p.Thr2465Ser variant was reported in two of 176 control alleles and is reported at a frequency of 0.01442 in the Japanese in Tokyo, Japan population of the 1000 Genomes Project; additionally, one homozygote is reported in the Latino population of the Genome Aggregation Database, though given the variability in disease presentation and age of onset, the presence of this individual in the database is not necessarily an argument against the potential pathogenicity of this variant. Based on the evidence, the p.Thr2465Ser variant is classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV001248752 | SCV001422260 | uncertain significance | not provided | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 2465 of the EYS protein (p.Thr2465Ser). This variant is present in population databases (rs145184183, gnomAD 0.1%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 26155838). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 632068). 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 tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
3billion | RCV001830668 | SCV002521150 | uncertain significance | Retinitis pigmentosa 25 | 2023-06-22 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.013%). Protein truncation variants are a common disease-causing mechanism. In silico tool predictions suggest no damaging effect of the variant on gene or gene product (REVEL: 0.19; 3Cnet: 0.11). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least 4 similarly affected unrelated individuals (PMID: 32218477). However, the variant has been reported as uncertain significance (ClinVar: VCV000632068.4) Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |
Natera, |
RCV001830668 | SCV002083522 | uncertain significance | Retinitis pigmentosa 25 | 2020-08-03 | no assertion criteria provided | clinical testing |