Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV003447875 | SCV004175795 | uncertain significance | Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 | 2023-02-14 | criteria provided, single submitter | clinical testing | The missense variant c.1060T>C (p.Phe354Leu) in the POLG2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency (0.0003%) in the gnomAD Exomes and novel in 1000 Genomes. The amino acid Phenylalanine at position 354 is changed to a Leucine changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Phe354Leu in POLG2 is predicted as conserved by PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |
Invitae | RCV003669423 | SCV004394827 | uncertain significance | not provided | 2024-01-23 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 354 of the POLG2 protein (p.Phe354Leu). This variant is present in population databases (rs551485718, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with POLG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2664901). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |