Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000726649 | SCV000701949 | uncertain significance | not provided | 2016-11-08 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000595275 | SCV000710851 | likely benign | not specified | 2016-05-02 | criteria provided, single submitter | clinical testing | p.Arg2573His in exon 41 of USH2A: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, >20 mammals have a histidine at this position despite high nearby amino a cid conservation. In addition, computational prediction tools do not suggest a h igh likelihood of impact to the protein. It has also been identified in 8/11572 Latino chromosomes and 24/66684 European chromosomes by the Exome Aggregation Co nsortium (ExAC, http://exac.broadinstitute.org; dbSNP rs189748047). |
Invitae | RCV000726649 | SCV001207176 | uncertain significance | not provided | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2573 of the USH2A protein (p.Arg2573His). This variant is present in population databases (rs189748047, gnomAD 0.04%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 20507924). ClinVar contains an entry for this variant (Variation ID: 497443). 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. 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. |
Gene |
RCV000726649 | SCV001814312 | uncertain significance | not provided | 2019-12-03 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |