Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000712799 | SCV000535357 | uncertain significance | not provided | 2018-08-06 | criteria provided, single submitter | clinical testing | The E1016K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E1016K variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E1016K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Eurofins Ntd Llc |
RCV000712799 | SCV000708805 | uncertain significance | not provided | 2017-05-23 | criteria provided, single submitter | clinical testing | |
| Athena Diagnostics | RCV000712799 | SCV000843330 | uncertain significance | not provided | 2017-12-15 | criteria provided, single submitter | clinical testing | |
| Wong Mito Lab, |
RCV000758319 | SCV000886978 | uncertain significance | Progressive sclerosing poliodystrophy | 2018-10-01 | criteria provided, single submitter | clinical testing | The NM_002693.2:c.3046G>A (NP_002684.1:p.Glu1016Lys) [GRCH38: NC_000015.10:g.89319286C>T] variant in POLG gene is interpretated to be a Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. PM2:This variant is absent in key population databases. Based on the evidence criteria codes applied, the variant is suggested to be Uncertain Significance. |
| Labcorp Genetics |
RCV000758319 | SCV001396004 | uncertain significance | Progressive sclerosing poliodystrophy | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1016 of the POLG protein (p.Glu1016Lys). This variant is present in population databases (rs763290547, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with POLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 392141). 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 POLG 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. |
| Mayo Clinic Laboratories, |
RCV000712799 | SCV005411121 | uncertain significance | not provided | 2024-07-22 | criteria provided, single submitter | clinical testing |