Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000041415 | SCV000065110 | likely pathogenic | Rare genetic deafness | 2011-10-03 | criteria provided, single submitter | clinical testing | The Asp458Val variant in USH1G has been identified as a homozygous variant in tw o Turkish probands with moderate to severe and profound hearing loss and was als o detected in 1/498 Turkish control chromosomes (Kalay 2005). In addition, the v ariant was also homozygous in four affected relatives of these probands, and 18 unaffected relatives were either heterozygous for the variant or were wild-type. The affected individuals in these two families were not reported to have vestib ular dysfunction, and did not report visual problems; however funduscopy suggest ed mild retinitis pigmentosa. Electroretinograms were not performed in affected individuals (Kalay 2005). In summary, this variant is likely to be pathogenic, t hough additional studies are required to fully establish its clinical significan ce. |
| Labcorp Genetics |
RCV001382883 | SCV001581838 | pathogenic | not provided | 2022-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 458 of the USH1G protein (p.Asp458Val). This variant is present in population databases (rs397517925, gnomAD 0.002%). This missense change has been observed in individual(s) with atypical Usher syndrome (PMID: 16283141, 28944237). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 48127). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). Experimental studies have shown that this missense change affects USH1G function (PMID: 20142502). For these reasons, this variant has been classified as Pathogenic. |
| Center of Genomic medicine, |
RCV001799509 | SCV001739292 | likely pathogenic | Usher syndrome type 1G | 2019-04-26 | criteria provided, single submitter | clinical testing | This variant was identified in an homozygous state in a young female patient profound hearing loss. It was inherited from both parents (asymptomatic heterozygous carriers). |
| Laboratory of Prof. |
RCV001799509 | SCV005073817 | pathogenic | Usher syndrome type 1G | 2024-06-10 | criteria provided, single submitter | research | Pathogenic by Deafness Variation Database based on PMID: 16283141 |