Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003079016 | SCV003459844 | pathogenic | not provided | 2022-09-06 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of USH2A-related conditions (PMID: 29641573, 31054281, 32188678, 32675063). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 disruptive. For these reasons, this variant has been classified as Pathogenic. This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 3444 of the USH2A protein (p.Cys3444Tyr). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003388149 | SCV003801312 | pathogenic | Usher syndrome | 2023-09-13 | criteria provided, single submitter | clinical testing | Variant summary: USH2A c.10331G>A (p.Cys3444Tyr) results in a non-conservative amino acid change located in the Fibronectin type III domain (IPR003961) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251280 control chromosomes (gnomAD). c.10331G>A has been reported in the literature as a biallelic compound heterozygous genotype in individuals affected with features of inherited retinal disease (IRD) such as Retinitis Pigmentosa (examples, Huang_2018, Gao_2021, Zhu_2021). These data indicate that the variant is very likely to be associated with disease. 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: 32188678, 29641573, 32675063). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Genome- |
RCV003455689 | SCV004182580 | pathogenic | Usher syndrome type 2A | 2023-11-04 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003465946 | SCV004208381 | likely pathogenic | Retinitis pigmentosa 39 | 2023-07-21 | criteria provided, single submitter | clinical testing |