ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.215A>G (p.Asn72Ser)

dbSNP: rs796052897
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000730674 SCV000242247 uncertain significance not provided 2013-04-24 criteria provided, single submitter clinical testing p.Asn72Ser (AAC>AGC): c.215 A>G in exon 2 of the POLG gene (NM_002693.2). The Asn72Ser missense change in the POLG gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Asn72Ser alters a highly conserved position in the DNA polymerase subunit gamma-1 protein and several in-silico algorithms predict it may be damaging to the structure/function of the protein. However, the amino acid substitution is conservative as both Asparagine and Serine are uncharged, polar amino acid residues. Therefore, based on the currently available information, it is unclear whether Asn72Ser is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Eurofins Ntd Llc (ga) RCV000730674 SCV000858428 uncertain significance not provided 2017-11-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003626609 SCV004513623 uncertain significance Progressive sclerosing poliodystrophy 2023-02-18 criteria provided, single submitter clinical testing 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. This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 72 of the POLG protein (p.Asn72Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 206567). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt POLG protein function.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.