Submissions for variant NM_002693.3(POLG):c.948G>A (p.Lys316=)

gnomAD frequency: 0.00259  dbSNP: rs61756401

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000118023	SCV000171131	benign	not specified	2013-04-04	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.
Eurofins Ntd Llc (ga)	RCV000118023	SCV000203328	benign	not specified	2015-06-17	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000433050	SCV000511544	likely benign	not provided	2017-01-11	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000118023	SCV000540099	likely benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: High allele frequency
Invitae	RCV000459441	SCV000556239	benign	Progressive sclerosing poliodystrophy	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002312232	SCV000846959	benign	Inborn genetic diseases	2016-06-23	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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	RCV000459441	SCV000887091	benign	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.948G>A (NP_002684.1:p.Lys316=) [GRCH38: NC_000015.10:g.89329018C>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). Based on the evidence criteria codes applied, the variant is suggested to be Benign.
Athena Diagnostics Inc	RCV000433050	SCV001145171	benign	not provided	2019-06-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001121510	SCV001280135	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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847714	SCV002104892	likely benign	Hereditary spastic paraplegia	2018-02-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000433050	SCV004137642	benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	POLG: BP4, BP7, BS1, BS2
Genetic Services Laboratory, University of Chicago	RCV000118023	SCV000152341	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000433050	SCV001741464	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000433050	SCV001930076	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000118023	SCV001973467	benign	not specified		no assertion criteria provided	clinical testing