Submissions for variant NM_002693.3(POLG):c.3708G>T (p.Gln1236His) (rs3087374)

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000118022	SCV000152340	benign	not specified	2013-08-29	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000118022	SCV000309150	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins NTD LLC (GA)	RCV000118022	SCV000340354	benign	not specified	2016-03-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services,Illumina	RCV000291582	SCV000394244	likely benign	Fanconi anemia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services,Illumina	RCV000327842	SCV000394245	benign	POLG-Related Spectrum Disorders	2018-03-06	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Ambry Genetics	RCV000715848	SCV000846679	benign	Seizures	2016-03-15	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	RCV000758401	SCV000887086	benign	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.3708G>T (NP_002684.1:p.Gln1236His) [GRCH38: NC_000015.10:g.89316763C>A] variant in FANCI 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 FANCI 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	RCV001000243	SCV001156794	benign	Fanconi anemia, complementation group I	2021-09-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services,Illumina	RCV001000243	SCV001279799	benign	Fanconi anemia, complementation group I	2018-03-06	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Athena Diagnostics Inc	RCV000118022	SCV001474647	benign	not specified	2020-03-02	criteria provided, single submitter	clinical testing
Invitae	RCV000758401	SCV001726587	benign	Progressive sclerosing poliodystrophy	2020-12-04	criteria provided, single submitter	clinical testing
Invitae	RCV000291582	SCV001726588	benign	Fanconi anemia	2020-12-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000676315	SCV001934735	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 31541998, 15917273, 21038416, 30255931)
GeneReviews	RCV000020480	SCV000040917	benign	Mitochondrial disease	2012-10-11	no assertion criteria provided	curation	Converted during submission to Benign.
Mayo Clinic Laboratories,Mayo Clinic	RCV000676315	SCV000802073	benign	not provided	2016-02-22	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000118022	SCV001743121	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000118022	SCV001808141	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000118022	SCV001928243	benign	not specified		no assertion criteria provided	clinical testing
Human Genetics - Radboudumc,Radboudumc	RCV000118022	SCV001957867	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000118022	SCV001974279	benign	not specified		no assertion criteria provided	clinical testing