Submissions for variant NM_002693.3(POLG):c.1066C>T (p.Leu356=)

gnomAD frequency: 0.00011  dbSNP: rs371431444

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127557	SCV000171134	benign	not specified	2013-06-07	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)	RCV000726665	SCV000345911	uncertain significance	not provided	2017-05-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000476514	SCV000556244	likely benign	Progressive sclerosing poliodystrophy	2024-01-29	criteria provided, single submitter	clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000476514	SCV000887009	likely benign	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.1066C>T (NP_002684.1:p.Leu356=) [GRCH38: NC_000015.10:g.89328789G>A] variant in POLG gene is interpretated to be a Likely 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). 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 Likely Benign.
Illumina Laboratory Services, Illumina	RCV001119513	SCV001277924	uncertain significance	POLG-Related Spectrum Disorders	2018-01-13	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Athena Diagnostics	RCV000726665	SCV001476777	likely benign	not provided	2020-07-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002408634	SCV002723111	likely benign	Inborn genetic diseases	2018-04-11	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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000726665	SCV004227466	uncertain significance	not provided	2023-03-01	criteria provided, single submitter	clinical testing	BP4
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000127557	SCV004803818	likely benign	not specified	2024-01-03	criteria provided, single submitter	clinical testing