Submissions for variant NM_002693.3(POLG):c.*122G>A (rs886051517)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel,ClinGen	RCV001526412	SCV001736750	uncertain significance	Mitochondrial disease	2021-05-07	reviewed by expert panel	curation	The c.122G>A (p.Arg42) variant in POLG has been observed in population database gnomAD at 0.03% (PM2). This variant has been observed in 1 case with another molecular cause - a large scale mitochondrial DNA deletion with clinical features of Kearns Sayre Syndrome (BP5; PMID: 21378381). In summary, there is not sufficient evidence to characterize this variant as pathogenic or benign, therefore it is characterized as a variant of uncertain significance for primary mitochondrial disease inherited in an autosomal recessive manner. ntDNA Mitochondrial ACMG-AMP Criteria for POLG applied: PM2, BP5.
Illumina Laboratory Services,Illumina	RCV000354186	SCV000394234	uncertain significance	Fanconi anemia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services,Illumina	RCV000259330	SCV000394235	uncertain significance	POLG-Related Spectrum Disorders	2018-01-12	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.
Illumina Laboratory Services,Illumina	RCV001119231	SCV001277588	uncertain significance	Fanconi anemia, complementation group I	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.