Submissions for variant NM_002693.3(POLG):c.3294T>C (p.Asn1098=)

gnomAD frequency: 0.00011  dbSNP: rs374224714

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen	RCV001526405	SCV001736743	uncertain significance	Mitochondrial disease	2021-05-06	reviewed by expert panel	curation	The c.3294T>C (p.Asn1098=) variant in POLG is present in population databases at the following frequencies: gnomAD Allele Frequency: 0.00028 with 0 homozygotes (PM2). This is a silent variant and no change in the amino acid (BP7). It has not been published in the literature. In summary, there is insufficient evidence to characterize this variant and therefore it remains a variant of uncertain significance for primary mitochondrial disease inherited in an autosomal recessive manner. ntDNA Mitochondrial ACMG-AMP Criteria for POLG applied: PM2, BP7
GeneDx	RCV000127536	SCV000171113	benign	not specified	2014-05-19	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.
PreventionGenetics, part of Exact Sciences	RCV000127536	SCV000309142	likely benign	not specified		criteria provided, single submitter	clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000758383	SCV000887058	likely benign	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.3294T>C (NP_002684.1:p.Asn1098=) [GRCH38: NC_000015.10:g.89318729A>G] 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000758383	SCV001010965	likely benign	Progressive sclerosing poliodystrophy	2024-01-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001171905	SCV001334801	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	POLG: BP4, BP7