Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetics, |
RCV001003373 | SCV001147009 | pathogenic | EMG: neuropathic changes; Microcephaly-complex motor and sensory axonal neuropathy syndrome | 2019-12-22 | criteria provided, single submitter | clinical testing | This is the first report of Tyr213His variant in VRK1 protein. It was found in homozygosis in a patient initially clinical diagnosed as Charcot-Marie-Tooth disease that leaded to a motor neuropathy or spinal muscular atrophy. It is a progressive disease affecting the lower motor neurons and characterized for a progressive muscle loss and weakness. Additionally, in vitro functional studies indicate that the Tyr213His is unable to phosphorylate several of its known substrates. Moreover, VRK1 (Y213H) was unable to form Cajal Bodies in human induced pluripotent stem cells of motor neurons. It is known that several mutations in VRK1 alters the dynamics of Cajal Bodies and that are related to neuromotor syndromes. Both function observed alterations meets our criteria to be classified as pathogenic. This patient, as shown the segregation studies, present the homozygous mutation inherit of consanguineous parents. |
| Fulgent Genetics, |
RCV002479197 | SCV002788656 | likely pathogenic | Pontocerebellar hypoplasia type 1A | 2021-08-04 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002479197 | SCV003461379 | uncertain significance | Pontocerebellar hypoplasia type 1A | 2024-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 213 of the VRK1 protein (p.Tyr213His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with spinal muscular atrophy (PMID: 32365420). ClinVar contains an entry for this variant (Variation ID: 812546). 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. Experimental studies have shown that this missense change affects VRK1 function (PMID: 32365420). 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. |