Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV001073804 | SCV001239366 | uncertain significance | Retinal dystrophy | 2018-04-11 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001245666 | SCV001418968 | likely pathogenic | not provided | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 4790 of the USH2A protein (p.Gln4790Pro). This variant is present in population databases (rs149807281, gnomAD 0.002%). This missense change has been observed in individuals with retinitis pigmentosa (Invitae). ClinVar contains an entry for this variant (Variation ID: 866070). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on USH2A protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Ocular Genomics Institute, |
RCV001376409 | SCV001573537 | uncertain significance | Retinitis pigmentosa 39 | 2021-04-08 | criteria provided, single submitter | research | The USH2A c.14369A>C 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. |
Gene |
RCV001245666 | SCV002031142 | uncertain significance | not provided | 2021-11-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002557899 | SCV003572447 | uncertain significance | Inborn genetic diseases | 2021-07-20 | criteria provided, single submitter | clinical testing | The c.14369A>C (p.Q4790P) alteration is located in exon 66 (coding exon 65) of the USH2A gene. This alteration results from a A to C substitution at nucleotide position 14369, causing the glutamine (Q) at amino acid position 4790 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001828535 | SCV002088225 | uncertain significance | Usher syndrome type 2A | 2020-09-21 | no assertion criteria provided | clinical testing |