Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001040316 | SCV001203880 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2019-12-14 | criteria provided, single submitter | clinical testing | 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with KIF1B-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with aspartic acid at codon 547 of the KIF1B protein (p.Val547Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid. |
| Ambry Genetics | RCV002400238 | SCV002704570 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-08 | criteria provided, single submitter | clinical testing | The p.V547D variant (also known as c.1640T>A) is located in coding exon 17 of the KIF1B gene. The valine at codon 547 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This change occurs in the first base pair of coding exon 17. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |