ClinVar Miner

Submissions for variant NM_002693.2(POLG):c.3597C>A (p.Thr1199=) (rs2307443)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel,ClinGen RCV001526406 SCV001736744 benign Mitochondrial diseases 2021-05-06 reviewed by expert panel curation The c.3597C>A (p.T1199=) variant in POLG is present in population databases ExAC at 1.269 (BA1; observed > 1% frequency). Computational prediction tool Revel unavailable given limited data. This variant was observed in homozygotes in 17 cases in gnomAD and 5 case in ExAC (BS2). This variant is a coding synonymous change (BP7). In summary, there is sufficient evidence to characterized this variant as a benign for primary mitochondrial disease inherited in an autosomal recessive manner. ntDNA Mitochondrial ACMG-AMP Criteria for POLG applied: BA1, BS2, BP7.
GeneDx RCV000127547 SCV000171124 benign not specified 2012-03-26 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000231024 SCV000287673 benign Progressive sclerosing poliodystrophy 2020-12-08 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000127547 SCV000309147 benign not specified criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000127547 SCV000614729 benign not specified 2017-07-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV000715742 SCV000846573 benign Seizures 2016-05-26 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification;Synonymous alterations with insufficient evidence to classify as benign
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000231024 SCV000887285 benign Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.3597C>A (NP_002684.1:p.Thr1199=) [GRCH38: NC_000015.10:g.89317422G>T] variant in POLG gene is interpretated to be a Benign based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. BS1:The minor allele frequency of this allele is high for Mitochondrial DNA depletion syndrome 4A (Alpers type). BS2:Observation of the variant in controls is inconsistent with penetrance of Mitochondrial DNA depletion syndrome 4A (Alpers type). BP4:Computational evidence/predictors indicate no impact on the POLG structure, function, or protein-protein interaction. BP7:The variant is silent with non predicted splice impact. Based on the evidence criteria codes applied, the variant is suggested to be Benign.
Illumina Clinical Services Laboratory,Illumina RCV001117760 SCV001275980 likely benign POLG-Related Spectrum Disorders 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Mayo Clinic Laboratories, Mayo Clinic RCV000676316 SCV000802074 benign not provided 2016-02-19 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000676316 SCV001743427 likely benign not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000127547 SCV001954420 benign not specified no assertion criteria provided clinical testing

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