Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV001753508 | SCV001994844 | uncertain significance | Mitochondrial disease | 2021-05-06 | reviewed by expert panel | curation | The c.3482-14 T>C variant in POLG is observed in population databases ExAC at 0.00007% and gnomAD 0.0005% (PM2; observed < 0.05% frequency). Computational prediction tool Revel not available given intronic variant. This variant has not been seen in homozygotes or published in the literature. In summary, there is not sufficient evidence to characterize this variant as pathogenic or benign, therefore it is characterized as a variant of uncertain significance for primary mitochondrial disease inherited in a autosomal recessive manner. ntDNA Mitochondrial ACMG-AMP Criteria for POLG applied: PM2. |
| Gene |
RCV000127544 | SCV000171121 | benign | not specified | 2014-03-28 | 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. |
| Labcorp Genetics |
RCV002055754 | SCV002421272 | likely benign | Progressive sclerosing poliodystrophy | 2023-12-20 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000127544 | SCV004099949 | likely benign | not specified | 2023-09-18 | criteria provided, single submitter | clinical testing | Variant summary: POLG c.3483-14T>C alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 6.8e-05 in 251070 control chromosomes (gnomAD). To our knowledge, no occurrence of c.3483-14T>C in individuals affected with POLG-Related Spectrum Disorders and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely benign, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |