Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000604697 | SCV000731484 | likely benign | not specified | 2017-03-07 | criteria provided, single submitter | clinical testing | p.Val2700Ile in exon 41 of USH2A: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. O f note, >10 mammals have an isoleucine (Ile) at this position despite high nearb y amino acid conservation. It has been identified in 1/66682 European chromosome s by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbS NP rs778655083). |
| Invitae | RCV002528774 | SCV002942517 | uncertain significance | not provided | 2022-02-24 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2700 of the USH2A protein (p.Val2700Ile). This variant is present in population databases (rs778655083, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 517281). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |