Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000800062 | SCV000939760 | uncertain significance | Familial aplasia of the vermis | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1069 of the AHI1 protein (p.Glu1069Gly). This variant is present in population databases (rs367640472, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with AHI1-related conditions. ClinVar contains an entry for this variant (Variation ID: 645894). 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 with a positive 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. |
Fulgent Genetics, |
RCV002507385 | SCV002814895 | uncertain significance | Joubert syndrome 3 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002537117 | SCV003750676 | uncertain significance | Inborn genetic diseases | 2022-01-19 | criteria provided, single submitter | clinical testing | The c.3206A>G (p.E1069G) alteration is located in exon 24 (coding exon 22) of the AHI1 gene. This alteration results from a A to G substitution at nucleotide position 3206, causing the glutamic acid (E) at amino acid position 1069 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |