Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
UW Hindbrain Malformation Research Program, |
RCV000201711 | SCV000256270 | pathogenic | Joubert syndrome 3 | 2015-02-23 | criteria provided, single submitter | research | |
Invitae | RCV001853231 | SCV002273846 | likely pathogenic | Joubert syndrome | 2021-11-09 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 659 of the AHI1 protein (p.Asp659Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Joubert syndrome (PMID: 26092869). ClinVar contains an entry for this variant (Variation ID: 217544). 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 expected to disrupt AHI1 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |