Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000725652 | SCV000338380 | uncertain significance | not provided | 2016-01-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000725652 | SCV000492090 | uncertain significance | not provided | 2016-12-01 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the AHI1 gene. The D25G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D25G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the D25G variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV001210085 | SCV001381551 | uncertain significance | Familial aplasia of the vermis | 2022-09-12 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 25 of the AHI1 protein (p.Asp25Gly). This variant is present in population databases (rs778792339, gnomAD 0.03%). 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: 285384). 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 AHI1 protein function. 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, |
RCV002503996 | SCV002815544 | uncertain significance | Joubert syndrome 3 | 2022-04-07 | criteria provided, single submitter | clinical testing |