Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001040567 | SCV001204149 | uncertain significance | Charcot-Marie-Tooth disease, type 2 | 2019-11-26 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with asparagine at codon 544 of the KIF1B protein (p.Ser544Asn). The serine residue is weakly conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs768672234, ExAC 0.01%). This variant has not been reported in the literature in individuals with KIF1B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Molecular Genetics Laboratory, |
RCV001173592 | SCV001336691 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |