ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.1840T>C (p.Tyr614His)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002643750 SCV003510866 uncertain significance Progressive sclerosing poliodystrophy 2024-10-28 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 614 of the POLG protein (p.Tyr614His). This variant is present in population databases (rs566520464, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of POLG-related conditions (PMID: 32613234). ClinVar contains an entry for this variant (Variation ID: 2192504). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 RCV003329462 SCV004036985 uncertain significance not provided 2023-09-19 criteria provided, single submitter clinical testing Heterozygous in an individual with Parkinson's disease who underwent whole exome sequencing (Zhao et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32613234)

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