ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.3400C>T (p.His1134Tyr)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002740529 SCV003017172 likely pathogenic Progressive sclerosing poliodystrophy 2022-11-29 criteria provided, single submitter clinical testing 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. This missense change has been observed in individual(s) with autosomal recessive POLG-related conditions (PMID: 33579567). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1134 of the POLG protein (p.His1134Tyr). Experimental studies have shown that this missense change affects POLG function (PMID: 33579567). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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