Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000309426 | SCV001385198 | pathogenic | not provided | 2023-06-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 5978 of the ADGRV1 protein (p.His5978Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Usher syndrome type 2 (PMID: 22147658, 30459346). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 289480). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001731567 | SCV001983677 | pathogenic | Usher syndrome | 2021-09-14 | criteria provided, single submitter | clinical testing | Variant summary: ADGRV1 c.17933A>G (p.His5978Arg) results in a non-conservative amino acid change located in the GPCR, family 2-like domain (IPR017981) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 248956 control chromosomes (gnomAD). c.17933A>G has been reported in the literature in multiple individuals affected with Usher Syndrome (e.g. Besnard_2012, Sloan-Heggen_2016, Fuster-Garcia_2018, Garcia-Garcia_2020). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic, while another ClinVar submitter (evaluation after 2014) cites it as uncertain significance. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Eurofins Ntd Llc |
RCV000309426 | SCV000343852 | uncertain significance | not provided | 2016-07-25 | flagged submission | clinical testing |