Submissions for variant NM_002693.3(POLG):c.134A>G (p.Gln45Arg)

gnomAD frequency: 0.00316  dbSNP: rs201016638

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000175733	SCV000227272	likely benign	not specified	2015-05-27	criteria provided, single submitter	clinical testing
GeneDx	RCV001711597	SCV000242142	likely benign	not provided	2020-12-04	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 19578034, 21880868)
Genetic Services Laboratory, University of Chicago	RCV000175733	SCV000248551	likely benign	not specified	2016-12-27	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000461738	SCV000556228	likely benign	Progressive sclerosing poliodystrophy	2025-01-30	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000175733	SCV000614700	benign	not specified	2020-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002314611	SCV000847653	likely benign	Inborn genetic diseases	2018-12-19	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000461738	SCV000887094	likely benign	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.134A>G (NP_002684.1:p.Gln45Arg) [GRCH38: NC_000015.10:g.89333621T>C] variant in POLG gene is interpretated to be a Likely Benign based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:19578034 . 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). BP3:This variant results in inframe indel in repeats without known function. BP4:Computational evidence/predictors indicate no impact on the POLG structure, function, or protein-protein interaction. Based on the evidence criteria codes applied, the variant is suggested to be Likely Benign.
Breakthrough Genomics, Breakthrough Genomics	RCV001711597	SCV005213952	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV003985739	SCV000309129	benign	POLG-related disorder	2022-09-02	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).