ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.2984A>G (p.Tyr995Cys)

gnomAD frequency: 0.00001  dbSNP: rs749458217
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000758464 SCV000887175 uncertain significance Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.2984A>G (NP_002684.1:p.Tyr995Cys) [GRCH38: NC_000015.10:g.89319348T>C] variant in POLG gene is interpretated to be a Uncertain Significance 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. PP2:This is a missense variant in POLG with a low rate of benign and high rate of pathogenic missense variations. Based on the evidence criteria codes applied, the variant is suggested to be Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000758464 SCV002224507 uncertain significance Progressive sclerosing poliodystrophy 2024-11-07 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 995 of the POLG protein (p.Tyr995Cys). This variant is present in population databases (rs749458217, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with POLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 619428). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.

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