ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.2884G>A (p.Ala962Thr)

gnomAD frequency: 0.00003  dbSNP: rs760305377
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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) RCV000731013 SCV000858783 uncertain significance not provided 2017-12-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001047525 SCV001211489 uncertain significance Progressive sclerosing poliodystrophy 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 962 of the POLG protein (p.Ala962Thr). This variant is present in population databases (rs760305377, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of POLG-related conditions (PMID: 21880868, 32005694, 32348839). ClinVar contains an entry for this variant (Variation ID: 595463). 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. 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.
GeneDx RCV000731013 SCV001985380 uncertain significance not provided 2020-09-25 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed with a pathogenic variant in a patient with ataxia, muscle weakness, and central hypoventilation in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Tang et al., 2011); This variant is associated with the following publications: (PMID: 21880868)
Mayo Clinic Laboratories, Mayo Clinic RCV000731013 SCV004227457 uncertain significance not provided 2023-06-23 criteria provided, single submitter clinical testing PP3, PM2, PM3_supporting

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