ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.3680C>A (p.Thr1227Asn)

gnomAD frequency: 0.00001  dbSNP: rs775517153
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000734457 SCV000862601 uncertain significance not provided 2018-07-24 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000758338 SCV000887003 uncertain significance Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.3680C>A (NP_002684.1:p.Thr1227Asn) [GRCH38: NC_000015.10:g.89316791G>T] 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. 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 Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000758338 SCV002246759 uncertain significance Progressive sclerosing poliodystrophy 2024-03-20 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1227 of the POLG protein (p.Thr1227Asn). This variant is present in population databases (rs775517153, gnomAD 0.002%). 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: 598136). 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 with a positive predictive value of 95%. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000734457 SCV002541290 uncertain significance not provided 2021-06-28 criteria provided, single submitter clinical testing

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