Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004063876 | SCV002732777 | uncertain significance | not specified | 2024-11-04 | criteria provided, single submitter | clinical testing | The p.S818T variant (also known as c.2452T>A), located in coding exon 23 of the KIF1B gene, results from a T to A substitution at nucleotide position 2452. The serine at codon 818 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
| Labcorp Genetics |
RCV003101837 | SCV003261116 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2024-05-22 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 818 of the KIF1B protein (p.Ser818Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KIF1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1791512). 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 KIF1B protein function with a negative predictive value of 80%. 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. |