Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000551325 | SCV002037597 | uncertain significance | Ethylmalonic encephalopathy | 2020-08-18 | reviewed by expert panel | curation | This variant was classified as a variant of uncertain significance as there has not been sufficient evidence to support either a benign or a pathogenic classification. Specifically, this variant has not been reported in the literature in affected or unaffected patients, has no published functional data. This variant is present in population databases with an allele frequency of 0.09%, which is higher allele frequency expected for a pathogenic variant in ETHE1 (BS1). However, not enough criteria were met to support a pathogenic or benign classification. |
Labcorp Genetics |
RCV000551325 | SCV000645213 | uncertain significance | Ethylmalonic encephalopathy | 2022-08-09 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 143 of the ETHE1 protein (p.Val143Ile). This variant is present in population databases (rs201846162, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with ETHE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 468478). 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 not expected to disrupt ETHE1 protein function. 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. |
Natera, |
RCV000551325 | SCV001456211 | uncertain significance | Ethylmalonic encephalopathy | 2019-10-28 | no assertion criteria provided | clinical testing |