Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000152572 | SCV000201825 | uncertain significance | not specified | 2017-07-05 | criteria provided, single submitter | clinical testing | The p.Arg4120Cys variant in USH2A has not been previously reported in individual s with hearing loss or Usher syndrome. This variant has been identified in 8/125 854 European chromosomes and 6/34358 Latino chromosomes by the genome Aggregatio n Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs727503718). Althou gh this variant has been seen in the general population, its frequency is not hi gh enough to rule out a pathogenic role. Computational prediction tools and con servation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, th e clinical significance of the p.Arg4120Cys variant is uncertain. |
Invitae | RCV001850079 | SCV002261796 | uncertain significance | not provided | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 4120 of the USH2A protein (p.Arg4120Cys). This variant is present in population databases (rs727503718, gnomAD 0.02%). This missense change has been observed in individual(s) with inherited retinal dystrophy (PMID: 32037395). ClinVar contains an entry for this variant (Variation ID: 166437). 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. 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. |
Genome- |
RCV003453117 | SCV004182012 | uncertain significance | Retinitis pigmentosa 39 | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001835692 | SCV004182013 | uncertain significance | Usher syndrome type 2A | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001835692 | SCV002088309 | uncertain significance | Usher syndrome type 2A | 2019-11-11 | no assertion criteria provided | clinical testing |