Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001052468 | SCV001216680 | pathogenic | not provided | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 2744 of the USH2A protein (p.Trp2744Cys). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 21686329, 26338283, 29625443, 29641573). 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: 848662). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Blueprint Genetics | RCV001075376 | SCV001240997 | pathogenic | Retinal dystrophy | 2018-06-12 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV001052468 | SCV002021609 | likely pathogenic | not provided | 2020-11-03 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003396674 | SCV004103001 | pathogenic | USH2A-related condition | 2024-01-02 | criteria provided, single submitter | clinical testing | The USH2A c.8232G>C variant is predicted to result in the amino acid substitution p.Trp2744Cys. This variant was reported in the compound heterozygous and homozygous states in multiple individuals with retinitis pigmentosa or Usher syndrome (Xu. 2011. PubMed ID: 21686329; Gao. 2021. PubMed ID: 32188678; Table S5, Huang. 2018. PubMed ID: 29641573; Sun. 2020. PubMed ID: 32100970). This variant is reported in 0.0055% of alleles in individuals of East Asian descent in gnomAD. This variant is interpreted as pathogenic. |
Genome- |
RCV003455229 | SCV004182829 | likely pathogenic | Retinitis pigmentosa 39 | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003455228 | SCV004182831 | likely pathogenic | Usher syndrome type 2A | 2023-11-04 | criteria provided, single submitter | clinical testing |