Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001226796 | SCV001399122 | uncertain significance | Hereditary spastic paraplegia 30; Neuropathy, hereditary sensory, type 2C; Intellectual disability, autosomal dominant 9 | 2024-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 421 of the KIF1A protein (p.His421Gln). This variant is present in population databases (rs369856336, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with KIF1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 954352). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt KIF1A 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. |
Gene |
RCV001773514 | SCV002003534 | uncertain significance | not provided | 2024-12-10 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; This amino acid substitution does not occur within the predicted motor domain of the protein, where most pathogenic missense variants in KIF1A have been identified (PMID: 25265257, 31488895).; In silico analysis indicates that this missense variant does not alter protein structure/function |