Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001064495 | SCV001229401 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2019-11-30 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with threonine at codon 1443 of the KIF1B protein (p.Ile1443Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with KIF1B-related conditions. This variant is not present in population databases (ExAC no frequency). |
Ambry Genetics | RCV003380835 | SCV004097755 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-13 | criteria provided, single submitter | clinical testing | The p.I1443T variant (also known as c.4328T>C), located in coding exon 39 of the KIF1B gene, results from a T to C substitution at nucleotide position 4328. The isoleucine at codon 1443 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |