Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000261805 | SCV000329666 | pathogenic | not provided | 2022-11-14 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 21880868, 21550804, 16919951, 21357833, 20185557, 28471437, 29655203, 30423451, 33671400, 34179544, 33511646, 30936349, 34052969, 33600046) |
Invitae | RCV000547242 | SCV000630128 | pathogenic | Progressive sclerosing poliodystrophy | 2023-12-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 807 of the POLG protein (p.Arg807Cys). This variant is present in population databases (rs769827124, gnomAD 0.02%). This missense change has been observed in individuals with autosomal recessive POLG-related disorders (PMID: 16919951, 21357833, 28471437). ClinVar contains an entry for this variant (Variation ID: 279982). 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%. Experimental studies have shown that this missense change affects POLG function (PMID: 20185557). This variant disrupts the p.Arg807 amino acid residue in POLG. Other variant(s) that disrupt this residue have been observed in individuals with POLG-related conditions (PMID: 14635118, 21880868, 28471437), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Genomic Research Center, |
RCV000626194 | SCV000746834 | pathogenic | Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 | 2017-12-18 | criteria provided, single submitter | clinical testing | |
Clinical Molecular Genetics Laboratory, |
RCV000678828 | SCV000805014 | uncertain significance | neonatal seizures | 2017-06-15 | criteria provided, single submitter | clinical testing | present with homozygous ALDH7A1 pathogenic variant |
Wong Mito Lab, |
RCV000547242 | SCV000887115 | pathogenic | Progressive sclerosing poliodystrophy | 2018-10-01 | criteria provided, single submitter | clinical testing | The NM_002693.2:c.2419C>T (NP_002684.1:p.Arg807Cys) [GRCH38: NC_000015.10:g.89322749G>A] variant in POLG gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:16919951 ; 21550804 . This variant meets the following evidence codes reported in the ACMG-guideline. PS1:This variation causes same amino-acid change as an established pathogenic variant. PS3:Well established functional studies show a deleterious effect on POLG. 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. 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 Pathogenic. |
Institute of Human Genetics, |
RCV001263147 | SCV001441225 | pathogenic | Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis | 2020-09-30 | criteria provided, single submitter | research | |
Ce |
RCV000261805 | SCV003917422 | pathogenic | not provided | 2023-04-01 | criteria provided, single submitter | clinical testing | POLG: PM1, PM2, PM3, PM5, PP3, PS3:Supporting |
Baylor Genetics | RCV000547242 | SCV004205907 | pathogenic | Progressive sclerosing poliodystrophy | 2023-04-27 | criteria provided, single submitter | clinical testing |