Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000607159 | SCV000712632 | uncertain significance | not specified | 2016-11-17 | criteria provided, single submitter | clinical testing | The p.Asn1235Ser variant in GPR98 has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified in 1/11278 of Lat ino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; dbSNP rs746622083). However, this frequency is not high enough to rul e out a pathogenic role. Computational prediction tools and conservation analysi s do not provide strong support for or against an impact to the protein. In summ ary, the clinical significance of the p.Asn1235Ser is uncertain. |
| Invitae | RCV001237864 | SCV001410646 | uncertain significance | not provided | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1235 of the ADGRV1 protein (p.Asn1235Ser). This variant is present in population databases (rs746622083, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 505432). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ADGRV1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |