ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.5901GGA[3] (p.Glu1969dup)

dbSNP: rs754275919
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000564148 SCV000671438 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-09 criteria provided, single submitter clinical testing The c.5904_5906dupGGA variant (also known as p.E1969dup), located in coding exon 43 of the POLE gene, results from an in-frame GGA duplication between nucleotide positions 5904 and 5906. This results in the duplication of an extra glutamic acid residue at codon 1969. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001764669 SCV001389830 uncertain significance not provided 2023-11-24 criteria provided, single submitter clinical testing This variant, c.5904_5906dup, results in the insertion of 1 amino acid(s) of the POLE protein (p.Glu1969dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs754275919, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 484458). 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.
GeneDx RCV001764669 SCV001998179 uncertain significance not provided 2019-10-10 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In-frame insertion of 1 amino acid in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function

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