Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001307288 | SCV001496693 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2020-03-09 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with alanine at codon 1225 of the KIF1B protein (p.Val1225Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs756516917, ExAC 0.006%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with KIF1B-related conditions. |
| Ambry Genetics | RCV002456392 | SCV002615857 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-30 | criteria provided, single submitter | clinical testing | The p.V1225A variant (also known as c.3674T>C), located in coding exon 33 of the KIF1B gene, results from a T to C substitution at nucleotide position 3674. The valine at codon 1225 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well 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. |