Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
UW Hindbrain Malformation Research Program, |
RCV000201537 | SCV000256271 | pathogenic | Joubert syndrome 3 | 2015-02-23 | criteria provided, single submitter | research | |
Invitae | RCV000817125 | SCV000957670 | uncertain significance | Joubert syndrome | 2018-10-11 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan with arginine at codon 725 of the AHI1 protein (p.Trp725Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Joubert syndrome (PMID: 16155189, 26092869). ClinVar contains an entry for this variant (Variation ID: 217545). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |