Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Wong Mito Lab, |
RCV000758310 | SCV000886968 | likely pathogenic | Progressive sclerosing poliodystrophy | 2018-10-01 | criteria provided, single submitter | clinical testing | The NM_002693.2:c.2606G>A (NP_002684.1:p.Arg869Gln) [GRCH38: NC_000015.10:g.89321253C>T] variant in POLG gene is interpretated to be a Likely Pathogenic based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. PM1:This variant is in mutational hot spot or a well-studied functional domain without benign variation. PM2:This variant is absent in key population databases. PM3:Detected in trans with a pathogenic variant for Mitochondrial DNA depletion syndrome 4A (Alpers type) which is a recessive disorder. PP1:This variant is co-segregated with Mitochondrial DNA depletion syndrome 4A (Alpers type) in multiple affected family members. PP2:This is a missense variant in POLG with a low rate of benign and high rate of pathogenic missense variations. PP3:Computational evidence/predictors indicate the variant has deleterious effect on POLG structure, function, or protein-protein interaction. PP4:Patient's phenotype or family history is highly specific for POLG. Based on the evidence criteria codes applied, the variant is suggested to be Likely Pathogenic. |
| Baylor Genetics | RCV000758310 | SCV004205923 | likely pathogenic | Progressive sclerosing poliodystrophy | 2023-02-27 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000758310 | SCV004353728 | pathogenic | Progressive sclerosing poliodystrophy | 2023-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 869 of the POLG protein (p.Arg869Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Autosomal recessive POLG-related conditions (PMID: 19578034, 21880868, 30818899, 31130284, 31665838). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 436357). 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 POLG protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV005004195 | SCV005633390 | likely pathogenic | Progressive sclerosing poliodystrophy; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1; Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis; Mitochondrial DNA depletion syndrome 4b | 2024-03-12 | criteria provided, single submitter | clinical testing | |
| Genetic Services Laboratory, |
RCV000503882 | SCV000596501 | uncertain significance | not specified | 2016-05-16 | flagged submission | clinical testing |