Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000214702 | SCV000271377 | pathogenic | Rare genetic deafness | 2015-06-23 | criteria provided, single submitter | clinical testing | The p.Arg2377X variant in GPR98 has been reported in one individual with Usher s yndrome type 2 (Besnard 2014). It has also been identified in 1/10908 South Asia n chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstit ute.org). Although this variant has been seen in the general population, its fr equency is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 2377, which is predicted to lead to a truncated or absent protein. In summary, this variant meets our criteria to be classified as pathogenic for hearing loss in an autosom al recessive manner (http://www.partners.org/personalizedmedicine/LMM) based upo n predicted impact to protein. |
Labcorp Genetics |
RCV003556278 | SCV004293578 | pathogenic | not provided | 2023-09-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg2377*) in the ADGRV1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADGRV1 are known to be pathogenic (PMID: 19357117, 22135276, 22147658, 26226137, 30718709, 31047384, 32467589). This variant is present in population databases (rs758718347, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 24498627). ClinVar contains an entry for this variant (Variation ID: 228353). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV003556278 | SCV005201910 | likely pathogenic | not provided | 2024-02-13 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31964843, 33749171, 24498627) |