Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000611584 | SCV000731571 | uncertain significance | not specified | 2017-04-28 | criteria provided, single submitter | clinical testing | The p.Gly310Glu (NM_032119.3 c.929G>A) variant in GPR98 (also known as ADGRV1) h as been reported in 1 individuals with Usher syndrome, who carried a second GPR9 8 variant if uncertain significance (Jiang 2015). This variant has been identifi ed in 0.1% (9/8626) of East Asian chromosomes by the Exome Aggregation Consortiu m (ExAC, http://exac.broadinstitute.org; dbSNP rs766790920). Although this varia nt has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation anal ysis suggest that the p.Gly310Glu variant may not impact the protein, though thi s information is not predictive enough to rule out pathogenicity. In summary, th e clinical significance of the p.Gly310Glu variant is uncertain. |
| Labcorp Genetics |
RCV001038199 | SCV001201660 | likely benign | not provided | 2024-08-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000611584 | SCV002511903 | uncertain significance | not specified | 2022-04-12 | criteria provided, single submitter | clinical testing | Variant summary: ADGRV1 c.929G>A (p.Gly310Glu) results in a non-conservative amino acid change located in the Na-Ca exchanger/integrin-beta4 domain (IPR003644) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.2e-05 in 249150 control chromosomes, predominantly at a frequency of 0.001 within the East Asian subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in ADGRV1 causing Usher Syndrome (9.2e-05 vs 0.0054), allowing no conclusion about variant significance. c.929G>A has been reported in the literature as a presumed compound heterozygous genotype in settings of multigene panel/WES analysis in at-least two East Asian individuals with Usher syndrome/Retinitis Pigmentosa (example, Jiang_2015, Wang_2018 and cited in Liu_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |