Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Personalized Medicine, |
RCV000735296 | SCV000854449 | likely pathogenic | Insomnia; Seizure; Ectopic tissue; Cerebral visual impairment; Hypoplasia of the corpus callosum; Microcephaly; Strabismus; Abnormal nonverbal communicative behavior; Short foot; Profound global developmental delay; Small hand | criteria provided, single submitter | clinical testing | ||
Invitae | RCV002535425 | SCV002185798 | uncertain significance | Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome | 2023-07-07 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 598953). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on QARS protein function. This missense change has been observed in individual(s) with progressive microcephaly with seizures and cerebral and cerebellar atrophy (PMID: 30755392). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 477 of the QARS protein (p.Tyr477Cys). |
Center for Personalized Medicine, |
RCV003156114 | SCV003845334 | likely pathogenic | See cases | 2022-12-21 | criteria provided, single submitter | clinical testing |