Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001376749 | SCV001573910 | pathogenic | not provided | 2024-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 4194 of the USH2A protein (p.Cys4194Arg). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with USH2A-related conditions (PMID: 25649381, 30029497, 33090715, 33124170; internal data). ClinVar contains an entry for this variant (Variation ID: 557093). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt USH2A protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003472152 | SCV004200751 | pathogenic | Retinitis pigmentosa 39 | 2024-01-16 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV003472152 | SCV005086675 | likely pathogenic | Retinitis pigmentosa 39 | 2023-07-16 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with retinitis pigmentosa 39 (MIM#613809) and Usher syndrome, type 2A (MIM#276901). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from cysteine to arginine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2 & v3: 3 heterozygotes, 0 homozygotes). (SP) 0309 - Multiple alternative amino acid changes at the same position have been observed in gnomAD (v2 & v3) (highest allele count: 2 heterozygotes, 0 homozygotes). (I) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0600 - Variant is located in the annotated Fibronectin type III domain (DECIPHER). (I) 0710 - Another missense variant comparable to the one identified in this case has inconclusive previous evidence for pathogenicity. p.(Cys4194Tyr) has been regarded as a VUS by multiple clinical laboratories in ClinVar. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. Even though it has been reported as a VUS (ClinVar, PMID: 33124170), this variant has been reported as likely pathogenic (ClinVar) and detected in multiple individuals with retinitis pigmentosa (PMIDs: 25649381, 30029497, 34315337, 33124170). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Counsyl | RCV000673184 | SCV000798359 | uncertain significance | Usher syndrome type 2A; Retinitis pigmentosa 39 | 2018-03-07 | flagged submission | clinical testing |