ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.2264A>C (p.Lys755Thr)

gnomAD frequency: 0.00004  dbSNP: rs770438363
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000598297 SCV000708424 uncertain significance not provided 2017-05-09 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000758303 SCV000886958 likely pathogenic Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.2264A>C (NP_002684.1:p.Lys755Thr) [GRCH38: NC_000015.10:g.89323405T>G] variant in POLG gene is interpretated to be a Likely Pathogenic based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. PS1:This variation causes same amino-acid change as an established pathogenic variant. PM2:This variant is absent in key population databases. Based on the evidence criteria codes applied, the variant is suggested to be Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000758303 SCV003480812 uncertain significance Progressive sclerosing poliodystrophy 2025-01-17 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 755 of the POLG protein (p.Lys755Thr). This variant is present in population databases (rs770438363, gnomAD 0.03%). 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: 501901). 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 disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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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