Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001306473 | SCV001495847 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2020-08-10 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with threonine at codon 1381 of the KIF1B protein (p.Ser1381Thr). The serine residue is moderately conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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. |
Ambry Genetics | RCV002327672 | SCV002627375 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-18 | criteria provided, single submitter | clinical testing | The p.S1381T variant (also known as c.4142G>C), located in coding exon 37 of the KIF1B gene, results from a G to C substitution at nucleotide position 4142. The serine at codon 1381 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |