Submissions for variant NM_002693.3(POLG):c.3075G>A (p.Leu1025=)

gnomAD frequency: 0.00008  dbSNP: rs146404260

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000230283	SCV000287670	likely benign	Progressive sclerosing poliodystrophy	2023-11-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001705260	SCV000514243	likely benign	not provided	2019-04-02	criteria provided, single submitter	clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000230283	SCV000887085	likely benign	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.3075G>A (NP_002684.1:p.Leu1025=) [GRCH38: NC_000015.10:g.89319257C>T] 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. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768051	SCV000898896	likely benign	Progressive sclerosing poliodystrophy; 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	2021-11-11	criteria provided, single submitter	clinical testing	POLG NM_002693 exon 19 p.Leu1025Leu (c.3075G>A): This variant has not been reported in the literature but is present in 11/126672 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs146404260). This variant is present in ClinVar (Variation ID:239380). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Center for Human Genetics Tuebingen	RCV001705260	SCV004137626	likely benign	not provided	2022-08-01	criteria provided, single submitter	clinical testing	POLG: BP4, BP7