Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001159300 | SCV001321002 | uncertain significance | Peroxisome biogenesis disorder 1A (Zellweger) | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Labcorp Genetics |
RCV002557363 | SCV003440069 | uncertain significance | Zellweger spectrum disorders | 2021-08-12 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with isoleucine at codon 242 of the PEX1 protein (p.Val242Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs764044654, ExAC 0.03%). This missense change has been observed in individual(s) with peroxisome biogenesis disorder although a second variant is not observed (PMID: 21846392). ClinVar contains an entry for this variant (Variation ID: 908690). 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 not expected to disrupt PEX1 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. |