Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000778294 | SCV000914472 | uncertain significance | Nephrotic syndrome, type 3 | 2018-11-22 | criteria provided, single submitter | clinical testing | The PLCE1 c.6377_6378delAA (p.Lys2126ArgfsTer17) variant results in a frameshift, and is predicted to result in premature termination of the protein. The p.Lys2126ArgfsTer17 variant has been reported in one study in which it is described in a compound heterozygous state with a missense variant in a female diagnosed with primary steroid resistant nephrotic syndrome at 31 months (Büscher et al. 2015). The p.Lys2126ArgfsTer17 variant was absent from 100 controls and is reported at a frequency of 0.002176 in the European American population of the Exome Sequencing Project. Based on the limited evidence and the potential impact of frameshift variants, the PLCE1 p.Lys2126ArgfsTer17 variant is classified as a variant of unknown significance but suspicious for pathogenicity for nephrotic syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Invitae | RCV003768422 | SCV004624006 | pathogenic | not provided | 2023-01-12 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs773902333, gnomAD 0.004%). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 631642). This premature translational stop signal has been observed in individual(s) with steroid-resistant nephrotic syndrome (SNRS) (PMID: 26668027). This sequence change creates a premature translational stop signal (p.Lys2126Argfs*17) in the PLCE1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PLCE1 are known to be pathogenic (PMID: 17086182, 20591883). |