Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Precision Medicine Center, |
RCV000019468 | SCV001593020 | likely pathogenic | Lipoprotein glomerulopathy | criteria provided, single submitter | research | PM2:at extremely low frequency in gnomAD PP2:Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease PP3:Multiple lines of computational evidence support a deleterious effect on the gene or gene product PP4:Patient's phenotype is highly specific for a disease | |
| Fulgent Genetics, |
RCV002496418 | SCV002813903 | likely pathogenic | Alzheimer disease 3; Alzheimer disease 2; Alzheimer disease 4; Age related macular degeneration 1; Sea-blue histiocyte syndrome; Lipoprotein glomerulopathy; Familial type 3 hyperlipoproteinemia | 2022-02-24 | criteria provided, single submitter | clinical testing | |
| 3billion, |
RCV000019468 | SCV004013623 | pathogenic | Lipoprotein glomerulopathy | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Missense changes are a common disease-causing mechanism. Functional studies provide moderate evidence of the variant having a damaging effect on the gene or gene product (PMID: 10432380). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.60; 3Cnet: 0.07). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000017880 / PMID: 10529625). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. | |
| Ambry Genetics | RCV004984646 | SCV005473007 | likely pathogenic | Cardiovascular phenotype | 2024-10-31 | criteria provided, single submitter | clinical testing | The p.R43C likely pathogenic variant (also known as c.127C>T), located in coding exon 2 of the APOE gene, results from a C to T substitution at nucleotide position 127. The arginine at codon 43 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant (also referred to as p.R25C, p.R69C, and APOE Kyoto) has been detected in numerous individuals, frequently of Asian ancestry, with features consistent with APOE-related lipoprotein glomerulopathy (LPG). However, this variant has also been detected in multiple unaffected individuals (Matsunaga A et al. Kidney Int, 1999 Aug;56:421-7; Wu Y et al. BMC Nephrol, 2013 Feb;14:53; Rovin BH et al. N Engl J Med, 2007 Dec;357:2522-4; Li W et al. Kidney Blood Press Res, 2014 Oct;39:330-9; Hu Z et al. Kidney Int, 2014 Feb;85:416-24; Usui R et al. CEN Case Rep, 2016 Nov;5:148-153; Katsarou M et al. J Lipid Res, 2018 Dec;59:2339-2348; Lui DTW et al. J Clin Lipidol, 2019 Dec;13:251-253; Yang M et al. Mol Genet Genomic Med, 2020 Aug;8:e1281; Song Y et al. Front Pediatr, 2021 Aug;9:684814; Zhu X et al. Front Med (Lausanne), 2022 Jul;9:885178; Wang R et al. J Med Case Rep, 2022 Feb;16:78; Qin Y et al. Ren Fail, 2024 Dec;46:2332491). This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic; however, it may exhibit reduced penetrance. |
| OMIM | RCV000019468 | SCV000039758 | pathogenic | Lipoprotein glomerulopathy | 2007-12-13 | no assertion criteria provided | literature only |