ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.3650C>T (p.Ala1217Val) (rs199751339)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766619 SCV000242255 uncertain significance not provided 2019-08-09 criteria provided, single submitter clinical testing Reported previously in an individual with sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) who had a second POLG variant identified as well as a variant in the SLC25A4 gene and a mtDNA deletion in muscle (Tanaka et al., 2013).; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 23524600, 27987238)
Athena Diagnostics Inc RCV000188632 SCV000614730 uncertain significance not specified 2017-03-28 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000758560 SCV000887303 uncertain significance Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.3650C>T (NP_002684.1:p.Ala1217Val) [GRCH38: NC_000015.10:g.89316821G>A] variant in FANCI gene is interpretated to be a Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. PP3:Computational evidence/predictors indicate the variant has deleterious effect on FANCI structure, function, or protein-protein interaction. Based on the evidence criteria codes applied, the variant is suggested to be Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000765233 SCV000896469 uncertain significance Progressive sclerosing poliodystrophy; Mitochondrial DNA depletion syndrome 1 (MNGIE type); Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1; Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis; Mitochondrial DNA depletion syndrome 4B, MNGIE type 2018-10-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001116313 SCV001274369 uncertain significance Fanconi anemia, complementation group I 2017-11-17 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services,Illumina RCV001116314 SCV001274370 uncertain significance POLG-Related Spectrum Disorders 2017-11-15 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV000758560 SCV001518280 uncertain significance Progressive sclerosing poliodystrophy 2020-10-08 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 1217 of the POLG protein (p.Ala1217Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs199751339, ExAC 0.06%). This variant has been observed in individual(s) with sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) (PMID: 23524600). ClinVar contains an entry for this variant (Variation ID: 206575). Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on POLG protein function (PMID: 27987238). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000766619 SCV001961529 uncertain significance not provided 2021-08-01 criteria provided, single submitter clinical testing

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