Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002741652 | SCV003026610 | uncertain significance | not provided | 2022-07-09 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs534853747, gnomAD 0.007%). 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) performed at Invitae indicates that this missense variant is expected to disrupt EARS2 protein function. This variant has not been reported in the literature in individuals affected with EARS2-related conditions. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 489 of the EARS2 protein (p.Arg489Trp). |
OMIM | RCV003487040 | SCV004242169 | pathogenic | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | 2024-01-26 | no assertion criteria provided | literature only |