Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000236524 | SCV000292742 | uncertain significance | not provided | 2015-03-13 | criteria provided, single submitter | clinical testing | The G836C variant in the KIF1A gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The G836C variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G836C 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. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this amino acid substitution does not occur within the predicted motor domain of the protein, where all pathogenic missense KIF1A mutations have been identified to-date (Lee et al., 2014). We interpret G836C as a variant of unknown significance. |
| Labcorp Genetics |
RCV001857796 | SCV002172783 | uncertain significance | Hereditary spastic paraplegia 30; Neuropathy, hereditary sensory, type 2C; Intellectual disability, autosomal dominant 9 | 2024-09-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 836 of the KIF1A protein (p.Gly836Cys). This variant is present in population databases (rs761671317, gnomAD 0.003%). 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: 245693). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KIF1A 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. |