Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002513043 | SCV003441697 | pathogenic | Progressive sclerosing poliodystrophy | 2023-07-17 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 864 of the POLG protein (p.Asn864Ser). This variant is present in population databases (rs121918050, gnomAD 0.007%). This missense change has been observed in individual(s) with autosomal recessive POLG-related conditions (PMID: 12825077, 30634555, 32005694). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13506). 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. Experimental studies have shown that this missense change affects POLG function (PMID: 20185557). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000014458 | SCV000034709 | pathogenic | Mitochondrial DNA depletion syndrome 4b | 2003-07-01 | no assertion criteria provided | literature only |