ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.1223AGC[2] (p.Gln410del)

dbSNP: rs765446994
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523737 SCV000617936 uncertain significance not provided 2015-12-04 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the POLG gene. The c.1229_1231delAGC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.1229_1231delAGC variant results in an in-frame deletion of a single Glutamine residue, denoted p.Gln410del. This deletion occurs at a position that is conserved in mammals. However, c.1229_1231delAGC is not predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000704825 SCV000833794 uncertain significance Progressive sclerosing poliodystrophy 2024-01-02 criteria provided, single submitter clinical testing This variant, c.1229_1231del, results in the deletion of 1 amino acid(s) of the POLG protein (p.Gln410del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs765446994, gnomAD 0.003%). 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: 449625). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000704825 SCV000887140 uncertain significance Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.1229_1231del (NP_002684.1:p.Gln410del) [GRCH38: NC_000015.10:g.89328482_89328484del] 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. PM2:This variant is absent in key population databases. BP3:This variant results in inframe indel in repeats without known function. Based on the evidence criteria codes applied, the variant is suggested to be Uncertain Significance.

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