Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001055417 | SCV000431345 | uncertain significance | Peroxisome biogenesis disorder 11A (Zellweger) | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV001055417 | SCV001219807 | uncertain significance | Peroxisome biogenesis disorder 11A (Zellweger) | 2022-09-05 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 11 of the PEX13 protein (p.Pro11Leu). This variant is present in population databases (rs564528921, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PEX13-related conditions. ClinVar contains an entry for this variant (Variation ID: 336662). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
| ARUP Laboratories, |
RCV001812877 | SCV002050264 | uncertain significance | not provided | 2021-09-13 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001812877 | SCV002063867 | uncertain significance | not provided | 2021-11-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002523137 | SCV003698189 | uncertain significance | Inborn genetic diseases | 2020-10-30 | criteria provided, single submitter | clinical testing | The c.32C>T (p.P11L) alteration is located in exon 1 (coding exon 1) of the PEX13 gene. This alteration results from a C to T substitution at nucleotide position 32, causing the proline (P) at amino acid position 11 to be replaced by a leucine (L). Based on data from the Genome Aggregation Database (gnomAD) database, the PEX13 c.32C>T alteration was observed in 0.01% (25/182820) of total alleles studied, with a frequency of 0.03% (21/72920) in the European (non-Finnish) subpopulation. This amino acid position is highly conserved in available vertebrate species. The p.P11L alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |