Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002536545 | SCV003262415 | uncertain significance | not provided | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 277 of the PISD protein (p.Arg277Gln). This variant is present in population databases (rs147371584, gnomAD 0.04%). This missense change has been observed in individual(s) with PISD-related conditions (PMID: 30858161). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 599401). 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) has been performed at Invitae 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 PISD protein function. Experimental studies have shown that this missense change affects PISD function (PMID: 30858161). 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. |
Clinical Genetics Research Group, |
RCV000786059 | SCV000863973 | likely pathogenic | PISD-related mitochondrial disease | 2019-01-10 | no assertion criteria provided | research | |
OMIM | RCV001095803 | SCV001251647 | pathogenic | Liberfarb syndrome | 2020-05-20 | no assertion criteria provided | literature only |