Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001844784 | SCV002104145 | uncertain significance | not specified | 2022-02-04 | criteria provided, single submitter | clinical testing | Variant summary: USH2A c.9259G>A (p.Val3087Ile) results in a conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.8e-05 in 251264 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in USH2A causing Usher Syndrome (8.8e-05 vs 0.011), allowing no conclusion about variant significance. c.9259G>A has been reported in the literature in individuals affected with deafness, retinal disease or usher syndrome (Miyagawa_2013, Huang_2015, Sun_2018, Guo_2021). 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV002543341 | SCV003519358 | pathogenic | not provided | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 3087 of the USH2A protein (p.Val3087Ile). This variant is present in population databases (rs200382994, gnomAD 0.1%). This missense change has been observed in individual(s) with USH2A-related conditions (PMID: 25356976, 29625443, 32675063, 33124170). 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: 1343767). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV002543341 | SCV004170459 | uncertain significance | not provided | 2023-04-11 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30245029, 23967202, 25356976, 29625443, 32188678, 33124170, 33708524, 32675063) |
| Baylor Genetics | RCV003464157 | SCV004208279 | uncertain significance | Retinitis pigmentosa 39 | 2023-12-19 | criteria provided, single submitter | clinical testing | |
| Dept Of Ophthalmology, |
RCV003888334 | SCV004707911 | likely benign | Retinal dystrophy | 2023-10-01 | criteria provided, single submitter | research | |
| Mayo Clinic Laboratories, |
RCV002543341 | SCV005408833 | uncertain significance | not provided | 2024-04-05 | criteria provided, single submitter | clinical testing | BS1_supporting, BP4, PM3_supporting |