ClinVar Miner

Submissions for variant NM_001134831.2(AHI1):c.2155G>C (p.Asp719His)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003495404 SCV004246376 likely pathogenic Familial aplasia of the vermis 2023-11-07 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 719 of the AHI1 protein (p.Asp719His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AHI1-related conditions. 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%. This variant disrupts the p.Asp719 amino acid residue in AHI1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16155189). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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