Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001897744 | SCV002157441 | uncertain significance | not provided | 2022-09-07 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1384647). 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 variant is present in population databases (rs201848368, gnomAD 0.05%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 82 of the EARS2 protein (p.Arg82Cys). |
3billion | RCV003152775 | SCV003841859 | uncertain significance | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.004%). Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (3Cnet: 0.98). Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline. |