Total submissions: 15
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetics and Genomic Medicine Centre, |
RCV000049851 | SCV005873636 | likely pathogenic | Finnish congenital nephrotic syndrome | 2021-01-19 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000049851 | SCV004191378 | pathogenic | Finnish congenital nephrotic syndrome | 2024-03-07 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001388275 | SCV004145519 | pathogenic | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | NPHS1: PM3:Very Strong, PM2, PS4:Moderate, PS3:Supporting, BP4 |
| Vasylyeva lab, |
RCV000049851 | SCV004123152 | pathogenic | Finnish congenital nephrotic syndrome | 2022-01-03 | criteria provided, single submitter | clinical testing | |
| Division of Human Genetics, |
RCV000049851 | SCV004024494 | pathogenic | Finnish congenital nephrotic syndrome | 2023-07-01 | criteria provided, single submitter | research | |
| Fulgent Genetics, |
RCV000049851 | SCV002781746 | pathogenic | Finnish congenital nephrotic syndrome | 2024-04-20 | criteria provided, single submitter | clinical testing | |
| Genome Diagnostics Laboratory, |
RCV002294008 | SCV002587197 | likely pathogenic | Kidney disorder | 2016-12-12 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV000049851 | SCV002059163 | pathogenic | Finnish congenital nephrotic syndrome | 2022-01-03 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000056438, PMID:11317351, PS1_S). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least 2 similarly affected unrelated individuals(PMID: 30655312, 21125408, 19194555, PM3_S). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Labcorp Genetics |
RCV001388275 | SCV001589205 | pathogenic | not provided | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 460 of the NPHS1 protein (p.Arg460Gln). This variant is present in population databases (rs386833880, gnomAD 0.003%). This missense change has been observed in individual(s) with nephrotic syndrome (PMID: 19194555, 21125408, 21415313, 30655312). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 56438). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000049851 | SCV000917904 | pathogenic | Finnish congenital nephrotic syndrome | 2017-09-14 | criteria provided, single submitter | clinical testing | Variant summary: The NPHS1 c.1379G>A (p.Arg460Gln) variant located in the Immunoglobulin-like fold domain (via InterPro) involves the alteration of a non-conserved nucleotide and 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 2/215308 control chromosomes at a frequency of 0.0000093, which does not exceed the estimated maximal expected allele frequency of a pathogenic NPHS1 variant (0.0033541). Multiple publications have cited the variant in homozygous and compound heterozygous affected pts. A functional study, Philippe_2008 indicates that the variant was shown to traffic normally in the cell and to homodimerize and to heterodimerize with NEPH1, but they suggest that additional studies are needed to evaluate whether missense variants that traffic to the membrane affect nephrin phosphorylation, actin reorganization in the cytoskeleton of podocytes, or downstream signaling events involved in transcriptional regulation and apoptosis. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic. |
| Illumina Laboratory Services, |
RCV000049851 | SCV000915829 | pathogenic | Finnish congenital nephrotic syndrome | 2017-07-20 | criteria provided, single submitter | clinical testing | Across a selection of the available literature, the NPHS1 c.1379G>A (p.Arg460Gln) variant has been identified in at least 11 individuals with congenital Finnish nephrosis. Specifically, the p.Arg460Gln variant was reported in a homozygous state in six individuals, in a compound heterozygous state in three individuals, and in a heterozygous state in two individuals (Sako et al. 2005; Heeringa et al. 2008; Lee et al. 2009; Machuca et al. 2010; Schoeb et al. 2010). The p.Arg460Gln variant was also found in a heterozygous state in the unaffected mother of an affected heterozygote (Sako et al. 2005). Two of the compound heterozygotes have null variants on the second allele (Heeringa et al. 2008; Machuca et al. 2010). Control data are unavailable for this variant, which is reported at a frequency of 0.000183 in the Other population of the Genome Aggregation Database but this is based on one allele so the variant is presumed to be rare. Based on the evidence, the p.Arg460Gln variant is classified as pathogenic for congenital nephrotic syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Counsyl | RCV000049851 | SCV000220658 | likely pathogenic | Finnish congenital nephrotic syndrome | 2014-08-29 | criteria provided, single submitter | literature only | |
| Yale Center for Mendelian Genomics, |
RCV001849302 | SCV002106846 | likely pathogenic | Nephrotic syndrome | 2017-11-10 | no assertion criteria provided | literature only | |
| Natera, |
RCV000049851 | SCV001460540 | pathogenic | Finnish congenital nephrotic syndrome | 2020-09-16 | no assertion criteria provided | clinical testing | |
| Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000049851 | SCV000082260 | likely pathogenic | Finnish congenital nephrotic syndrome | no assertion criteria provided | not provided | Converted during submission from probable-pathogenic to Likely pathogenic. |