Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000844604 | SCV000731305 | pathogenic | Rare genetic deafness | 2016-11-23 | criteria provided, single submitter | clinical testing | The p.Arg2336X variant in GPR98 has been previously reported in 1 Chinese indivi dual with Usher syndrome who was compound heterozygous for a second truncating v ariant in GPR98 (Jiang 2015). This variant has not been identified in large pop ulation studies. This nonsense variant leads to a premature termination codon at position 2336, which is predicted to lead to a truncated or absent protein. Los s of GPR98 function is an established disease mechanism in autosomal recessive U sher syndrome. In summary, this variant meets criteria to be classified as patho genic for autosomal recessive Usher syndrome based upon the predicted impact to the protein. |
| Invitae | RCV001849954 | SCV002245919 | pathogenic | not provided | 2022-07-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg2336*) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 143160). This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 26338283). |
| Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000132687 | SCV002820234 | pathogenic | Usher syndrome type 2C | criteria provided, single submitter | clinical testing | The stop gained p.R2336* in ADGRV1 (NM_032119.4) has been previously reported in 1 Chinese individual with Usher syndrome (Jiang et al, 2015). This variant is predicted to cause loss of normal protein function through protein truncation. The p.R2336* variant is a loss of function variant in the gene ADGRV1, which is intolerant of Loss of Function variants. The amino acid change p.Arg2336Ter in ADGRV1 is predicted as conserved by GERP++ across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. | |
| Department of Ophthalmology and Visual Sciences Kyoto University | RCV000132687 | SCV000172640 | probable-pathogenic | Usher syndrome type 2C | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |