Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000188544 | SCV000242162 | likely benign | not specified | 2012-08-08 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
| Eurofins Ntd Llc |
RCV000727522 | SCV000709444 | uncertain significance | not provided | 2017-06-16 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001044308 | SCV001208099 | uncertain significance | Progressive sclerosing poliodystrophy | 2024-03-04 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 194 of the POLG protein (p.Ala194Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 206493). 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. |
| Ambry Genetics | RCV002354530 | SCV002648280 | uncertain significance | Inborn genetic diseases | 2020-03-26 | criteria provided, single submitter | clinical testing | The p.A194V variant (also known as c.581C>T), located in coding exon 1 of the POLG gene, results from a C to T substitution at nucleotide position 581. The alanine at codon 194 is replaced by valine, an amino acid with similar properties. This alteration was detected once as heterozygous in an individual with inclusion body myositis (IBM) (Lindgren U et al. Neuromuscul. Disord., 2015 Apr;25:281-8). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |