Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001213066 | SCV001384682 | pathogenic | not provided | 2022-07-05 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1608 of the USH2A protein (p.His1608Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of retinitis pigmentosa and/or Usher syndrome (PMID: 23591405; Invitae). 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: 942974). 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. This variant disrupts the p.His1608 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been observed in individuals with USH2A-related conditions (PMID: 32675063; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Institute of Human Genetics, |
RCV004813891 | SCV005071149 | likely pathogenic | Retinal dystrophy | 2019-01-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005236688 | SCV005883645 | uncertain significance | not specified | 2024-12-12 | criteria provided, single submitter | clinical testing | Variant summary: USH2A c.4823A>G (p.His1608Arg) results in a non-conservative amino acid change located in the Laminin G domain (IPR001791) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251030 control chromosomes. c.4823A>G has been reported in the literature in individuals affected with Usher Syndrome and/or retinitis pigmentosa (e.g. Glockle_2014, Weisschuh_2020, Labcorp(formerly Invitae)). These data indicate that the variant may 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: 23591405, 32531858). ClinVar contains an entry for this variant (Variation ID: 942974). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |