Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001244399 | SCV001417619 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-11-11 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 959 of the KIF1B protein (p.Phe959Val). This variant is present in population databases (rs142096228, gnomAD 0.0009%). 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: 969127). 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. |
Ambry Genetics | RCV002436961 | SCV002749545 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-15 | criteria provided, single submitter | clinical testing | The p.F959V variant (also known as c.2875T>G), located in coding exon 25 of the KIF1B gene, results from a T to G substitution at nucleotide position 2875. The phenylalanine at codon 959 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |