Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000308238 | SCV000338419 | uncertain significance | not provided | 2015-12-17 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000308238 | SCV001402683 | pathogenic | not provided | 2023-02-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 605 of the USH2A protein (p.Cys605Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of USH2A-related conditions (PMID: 25472526; Invitae). ClinVar contains an entry for this variant (Variation ID: 285412). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt USH2A protein function. |
| Broad Center for Mendelian Genomics, |
RCV001723872 | SCV001950400 | uncertain significance | Retinitis pigmentosa | 2021-04-01 | criteria provided, single submitter | curation | The p.Cys605Arg variant in USH2A was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PM3-P. Based on this evidence we have classified this variant as a Variant of Uncertain Significance. If you have any questions about the classification please reach out to the Pierce Lab. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323493 | SCV004029983 | likely pathogenic | Usher syndrome | 2023-07-21 | criteria provided, single submitter | clinical testing | Variant summary: USH2A c.1813T>C (p.Cys605Arg) results in a non-conservative amino acid change to a highly conserved residue (HGMD) located in the Laminin-type EGF domain (IPR002049) 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 251348 control chromosomes (gnomAD). c.1813T>C has been reported in the literature in individuals affected with retinitis pigmentosa or Usher Syndrome (Zhao_2015, Hufnagel_2022), and at least one was reported as compound heterozygous with another pathogenic variant. These data indicate that the variant is 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: 25472526, 35266249). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as pathogenic (n=1) or uncertain significance (n=2). Based on the evidence outlined above, the variant was classified as likely pathogenic. |