ClinVar Miner

Submissions for variant NM_002693.2(POLG):c.3286C>T (p.Arg1096Cys) (rs201732356)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000758420 SCV000891542 likely pathogenic Progressive sclerosing poliodystrophy 2017-12-30 criteria provided, single submitter curation
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000188613 SCV000706348 pathogenic not provided 2017-02-08 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762952 SCV000893384 likely pathogenic Progressive sclerosing poliodystrophy; Mitochondrial DNA depletion syndrome 1 (MNGIE type); Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 1; Cerebellar ataxia infantile with progressive external ophthalmoplegia; Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis; Mitochondrial DNA depletion syndrome 4B, MNGIE type 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000188613 SCV000242236 pathogenic not provided 2018-08-02 criteria provided, single submitter clinical testing The R1096C variant in the POLG gene has been reported previously in multiple patients with Alpers syndrome, a clinical presentation suggestive of POLG deficiency, or progressive external ophthalmoplegia (arPEO) and peripheral neuropathy, who were either homozygous for the R1096C variant (Mohamed et al., 2011; Wong et al, 2008; Tang et al., 2011; Ashley et al. 2008) or compound heterozygous for the R1096C variant and another pathogenic variant (Tang et al., 2011; Ashley et al., 2008; Lax et al., 2012).
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000758420 SCV000887123 pathogenic Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.3286C>T (NP_002684.1:p.Arg1096Cys) [GRCH38: NC_000015.10:g.89318737G>A] variant in POLG gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:12707443 ; 21305355 . This variant meets the following evidence codes reported in the ACMG-guideline. PS1:This variation causes same amino-acid change as an established pathogenic variant. PS3:Well established functional studies show a deleterious effect on POLG. PM2:This variant is absent in key population databases. PM3:Detected in trans with a pathogenic variant for Mitochondrial DNA depletion syndrome 4A (Alpers type) which is a recessive disorder. PP1:This variant is co-segregated with Mitochondrial DNA depletion syndrome 4A (Alpers type) in multiple affected family members. PP4:Patient's phenotype or family history is highly specific for POLG. Based on the evidence criteria codes applied, the variant is suggested to be Pathogenic.

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