Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004051210 | SCV002630168 | uncertain significance | not specified | 2023-03-30 | criteria provided, single submitter | clinical testing | The c.1163-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 12 of the KIF1B gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, the evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
Labcorp Genetics |
RCV003102510 | SCV003284704 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-11-10 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 12 of the KIF1B gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in KIF1B cause disease. This variant is present in population databases (rs775090163, gnomAD 0.002%). 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: 1737388). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
Fulgent Genetics, |
RCV005042808 | SCV005669939 | uncertain significance | Charcot-Marie-Tooth disease type 2A1; Neuroblastoma, susceptibility to, 1 | 2024-06-18 | criteria provided, single submitter | clinical testing |