CMT2; CMT2A; CMT2A1; HMSNII; KLP; NBLST1
The KIF1B gene currently has no well-established disease association; however, there is preliminary evidence supporting a correlation with autosomal dominant susceptibility to hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndrome (PMID: 24694336), neuroblastoma (PMID: 18614535, 18334619, 24469107), and Charcot-Marie-Tooth disease (CMT) (PMID: 30373780).
Order this gene as a single gene test.
KIF1B: Sequencing analysis for exons 20, 30 includes only cds +/- 10 bp.
Invitae tests that include this gene:
The KIF1B gene encodes a protein called kinesin family member 1B, part of the kinesin family proteins that are essential for transporting materials within cells. Kinesin family member 1B specialized in transporting mitochondria and, in neurons, synaptic vesicles.
While there is currently no well-established data to associate the KIF1B gene with a specific disease or condition, there is preliminary evidence suggesting variants in this gene may be associated with a predisposition to paraganglioma-pheochromocytoma syndrome (PMID: 25263965, 19092153, 20959442, 24694336, 24899893, 24903423, 26347711, 24523625, 25385035, 26839173) and neuroblastoma (PMID: 24903423, 26347711, 24523625, 18614535, 26839173). These data, however, are currently insufficient to make a clear determination regarding this association. Therefore, KIF1B is available as a “preliminary-evidence” gene on Invitae’s Hereditary Paraganglioma-Pheochromocytoma Panel and Nervous System/Brain Cancer Panel. Preliminary-evidence genes are selected from an extensive review of the literature and expert recommendations, but the association between the gene and the specific condition has not been completely established. This uncertainty may be resolved as new information becomes available, and therefore clinicians may continue to order these preliminary-evidence genes.
The KIF1B gene encodes a protein called kinesin family member 1B, part of the kinesin family proteins that are essential for transporting materials within cells. Kinesin family member 1B specialized in transporting mitochondria and, in neurons, synaptic vesicles. In addition to its transport functions, the kinesin family member 1B protein appears to be involved in apoptosis (National Library of Medicine. Genetics Home Reference. KIF1B. Accessed March 2016., NCBI. Gene. Gene ID: 23095. Accessed March 2016).
Variants in KIF1B have autosomal dominant inheritance. This means that an individual with a pathogenic variant has a 50% chance of passing that variant on to their offspring.
Because the evidence regarding KIF1B and paraganglioma-pheochromocytoma syndrome and neuroblastoma is limited and preliminary, there are currently no guidelines or recommendations to suggest alteration to medical management based solely on the presence of an KIF1B variant. However, an individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors including personal medical history, family history as well as available genetic information that may result in a personalized plan for cancer prevention and surveillance.
Even though data regarding KIF1B is limited, knowing if a pathogenic variant is present is advantageous. Relatives can be identified, allowing pursuit of a diagnostic evaluation. In addition, the available information regarding hereditary cancer susceptibility genes is constantly evolving and clinically relevant KIF1B data is likely to become available in the near future. Awareness of this variant allows patients and their providers to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information, inform at-risk family members, and diligently follow standard screening protocols.
Review date: July 2016
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|
*KIF1B: Sequencing analysis for exons 20, 30 includes only cds +/- 10 bp.