Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000615962 | SCV000712390 | likely pathogenic | Rare genetic deafness | 2016-08-18 | criteria provided, single submitter | clinical testing | The p.Arg262X variant in GRXCR1 has been reported in one individual with hearing loss and segregated with disease in one affected relative (Mori 2015). Both ind ividuals also harbored a second GRXCR1 variant on the remaining copy of the gene . This variant has been identified in 2/8614 East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs761349153 ). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 262, which is locate d in the last exon and is more likely to escape nonsense mediated decay (NMD) an d result in a truncated protein. The GRXCR1 gene contains four exons, and the l ast exon is highly conserved; however, truncating variants have not been reporte d 3' of the p.Arg262X variant. In summary, although additional studies are requi red to fully establish its clinical significance, the p.Arg262X variant is likel y pathogenic for autosomal recessive hearing loss. |
Labcorp Genetics |
RCV001860247 | SCV002307881 | likely pathogenic | not provided | 2023-03-31 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 505242). 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. This premature translational stop signal has been observed in individuals with deafness (PMID: 25802247, 31389194). This variant is present in population databases (rs761349153, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Arg262*) in the GRXCR1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 29 amino acid(s) of the GRXCR1 protein. |