Submissions for variant NM_002693.3(POLG):c.1174C>G (p.Leu392Val)

gnomAD frequency: 0.00194  dbSNP: rs145289229

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000188651	SCV000231656	likely benign	not specified	2018-04-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000710181	SCV000242274	likely benign	not provided	2020-09-24	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in 0.1774% (501/282492 alleles) in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 18546365, 31669236, 20434700, 25462018, 21880868, 25118206, 17846414, 23251356, 29341116)
Invitae	RCV000475753	SCV000556247	likely benign	Progressive sclerosing poliodystrophy	2024-01-29	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000515415	SCV000611501	uncertain significance	Progressive sclerosing poliodystrophy; Mitochondrial DNA depletion syndrome 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1; Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis; Mitochondrial DNA depletion syndrome 4b	2017-05-23	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000188651	SCV000614699	benign	not specified	2021-05-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002317054	SCV000851083	likely benign	Inborn genetic diseases	2018-12-07	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	RCV000475753	SCV000887092	likely benign	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.1174C>G (NP_002684.1:p.Leu392Val) [GRCH38: NC_000015.10:g.89328532G>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:20434700 ; 21880868 . This variant meets the following evidence codes reported in the ACMG-guideline. BP2:The variant is observed in trans/cis with a dominant variant. 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.
Illumina Laboratory Services, Illumina	RCV001119511	SCV001277922	benign	POLG-Related Spectrum Disorders	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000710181	SCV001501094	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	POLG: PM2, BS2
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847818	SCV002105541	uncertain significance	Hereditary spastic paraplegia	2020-09-29	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003985741	SCV004740795	likely benign	POLG-related disorder	2022-04-22	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000710181	SCV001742752	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000710181	SCV001955732	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000710181	SCV001968634	uncertain significance	not provided		no assertion criteria provided	clinical testing