ClinVar Miner

Submissions for variant NM_002693.2(POLG):c.2254C>T (p.Leu752=) (rs41564016)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000118013 SCV000171098 benign not specified 2011-09-15 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,PreventionGenetics RCV000118013 SCV000309134 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000275068 SCV000394278 likely benign 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 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.
Invitae RCV000464149 SCV000556231 benign Progressive sclerosing poliodystrophy 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000715837 SCV000846668 likely benign Seizures 2016-05-26 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000464149 SCV000887078 benign Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.2254C>T (NP_002684.1:p.Leu752=) [GRCH38: NC_000015.10:g.89323415G>A] 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). 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 Benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000118013 SCV001156801 benign not specified 2019-06-04 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000118013 SCV000152331 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.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000676324 SCV000802085 benign not provided 2016-02-29 no assertion criteria provided clinical testing

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