Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000351008 | SCV000346715 | uncertain significance | Neuroblastoma | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Ce |
RCV000993907 | SCV001147132 | uncertain significance | not provided | 2016-06-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000392725 | SCV001234292 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2024-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1376 of the KIF1B protein (p.Arg1376His). This variant is present in population databases (rs149417293, gnomAD 0.006%). 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: 291580). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Institute for Clinical Genetics, |
RCV000993907 | SCV002011653 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004021348 | SCV002628532 | uncertain significance | not specified | 2024-09-30 | criteria provided, single submitter | clinical testing | The p.R1376H variant (also known as c.4127G>A), located in coding exon 37 of the KIF1B gene, results from a G to A substitution at nucleotide position 4127. The arginine at codon 1376 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
| St. |
RCV004786661 | SCV005402158 | uncertain significance | Neuroblastoma, susceptibility to, 1 | 2024-04-03 | criteria provided, single submitter | clinical testing | The KIF1B c.4127G>A (p.Arg1376His) missense change has a maximum subpopulation frequency of 0.005% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with pheochromocytoma or neuroblastoma. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |