Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001108777 | SCV001266052 | uncertain significance | Nephrotic syndrome, type 3 | 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. |
| Fulgent Genetics, |
RCV001108777 | SCV002779185 | uncertain significance | Nephrotic syndrome, type 3 | 2022-03-30 | criteria provided, single submitter | clinical testing | |
| Neuberg Centre For Genomic Medicine, |
RCV001108777 | SCV005373552 | pathogenic | Nephrotic syndrome, type 3 | 2023-06-02 | criteria provided, single submitter | clinical testing | The observed missense c.1081T>C (p.Trp361Arg) variant in PLCE1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Trp361Arg variant is present with allele frequency of 0.02% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance. Computational evidence (Polyphen - Benign, SIFT - Damaging and MutationTaster - Polymorphism) predicts conflicting evidence on protein structure and function for this variant. The reference amino acid of p.Trp361Arg in PLCE1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Trp at position 361 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS). In absence of another reportable variant in PLCE1 gene, the molecular diagnosis is not confirmed. |