ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.1735C>T (p.Arg579Trp)

gnomAD frequency: 0.00002  dbSNP: rs556925652
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000544202 SCV000630108 pathogenic Progressive sclerosing poliodystrophy 2023-12-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 579 of the POLG protein (p.Arg579Trp). This variant is present in population databases (rs556925652, gnomAD 0.01%). This missense change has been observed in individuals with autosomal recessive POLG-related conditions (PMID: 12975295, 33486010). ClinVar contains an entry for this variant (Variation ID: 458695). 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.
GeneDx RCV001584248 SCV001812319 likely pathogenic not provided 2023-02-23 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12975295, Alghtani_Article, 33486010)
Athena Diagnostics RCV001584248 SCV001879829 uncertain significance not provided 2020-09-22 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001584248 SCV004137637 uncertain significance not provided 2023-03-01 criteria provided, single submitter clinical testing POLG: PM2
Baylor Genetics RCV000544202 SCV005056571 likely pathogenic Progressive sclerosing poliodystrophy 2024-02-28 criteria provided, single submitter clinical testing

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