Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001318146 | SCV001508837 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2020-09-26 | 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: "Tolerated"; 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 arginine with histidine at codon 1171 of the KIF1B protein (p.Arg1171His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. |
Ambry Genetics | RCV002456426 | SCV002616373 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-03 | criteria provided, single submitter | clinical testing | The p.R1171H variant (also known as c.3512G>A), located in coding exon 31 of the KIF1B gene, results from a G to A substitution at nucleotide position 3512. The arginine at codon 1171 is replaced by histidine, an amino acid with highly similar properties. This alteration was detected in a patient with failure to thrive, motor and speech delay, ataxia, dystonia, and spastic paraplegia from a cohort of greater than 2200 Saudi patients who underwent whole exome sequencing (Monies D et al. Am J Hum Genet, 2019 06;104:1182-1201). This amino acid position is highly conserved in available vertebrate species. 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. |
Revvity Omics, |
RCV003485707 | SCV003814571 | uncertain significance | Charcot-Marie-Tooth disease type 2A1 | 2019-04-04 | criteria provided, single submitter | clinical testing |