Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000041718 | SCV000065414 | uncertain significance | not specified | 2011-04-08 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Ser4111Phe vari ant in USH2A has not been reported in the literature; however, this variant has been identified by our laboratory in two other individual with hearing loss; nei ther of whom had a second USH2A variant. Computational analyses (biochemical ami no acid properties, homology, PolyPhen2, SIFT, AlignGVGD) do not provide strong support for or against pathogenicity. In summary, the clinical significance of t his variant cannot be determined with certainty at this time; however, based upo n this data we would lean towards a more likely benign interpretation. |
Invitae | RCV001241616 | SCV001414646 | pathogenic | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 4111 of the USH2A protein (p.Ser4111Phe). This variant is present in population databases (rs142095945, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of USH2A-related conditions ‚Äã (PMID: 30902645, 32037395; 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: 48396). 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 not expected to disrupt USH2A protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Department of Genetics, |
RCV001270357 | SCV001450584 | uncertain significance | Retinitis pigmentosa | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs142095945, gnomAD_exomes 0.008%), missense variant in a gene that has a low rate of benign missense variation, predicted benign by in-silico pathogenicity predictors. (ACMG: PM2 Moderate, PP2 Supporting, BP4 Supporting). Found in trans with variant NM_206933:c.12332C>T) | |
Ocular Genomics Institute, |
RCV001376289 | SCV001573379 | uncertain significance | Retinitis pigmentosa 39 | 2021-04-08 | criteria provided, single submitter | research | The USH2A c.12332C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2. Based on this evidence we have classified this variant as Variant of Uncertain Significance. |
Fulgent Genetics, |
RCV002496660 | SCV002816042 | uncertain significance | Usher syndrome type 2A; Retinitis pigmentosa 39 | 2021-08-22 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV001376289 | SCV004208178 | likely pathogenic | Retinitis pigmentosa 39 | 2023-10-14 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001274935 | SCV001459517 | uncertain significance | Usher syndrome type 2A | 2019-11-11 | no assertion criteria provided | clinical testing |