Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000041766 | SCV000065462 | likely benign | not specified | 2015-08-04 | criteria provided, single submitter | clinical testing | p.Thr4844Met in exon 66 of USH2A: This variant has been reported in the heterozy gous state in one individual with nonsyndromic retinitis pigmentosa, but a varia nt on the second allele was not identified (McGee 2010). It is not expected to h ave clinical significance due to a lack of conservation across species, includin g mammals. Of note, several mammals carry a methionine (Met) at this position de spite high nearby amino acid conservation. The p.Thr4844Met variant has also bee n identified in 4/11578 Latino chromosomes by the Exome Aggregation Consortium ( ExAC, http://exac.broadinstitute.org; dbSNP rs200570742). |
Gene |
RCV001038994 | SCV000714909 | likely benign | not provided | 2020-11-30 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 20507924) |
Invitae | RCV001038994 | SCV001202500 | uncertain significance | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 4844 of the USH2A protein (p.Thr4844Met). This variant is present in population databases (rs200570742, gnomAD 0.03%). 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: 48443). 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. |