Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001757897 | SCV001987870 | uncertain significance | not provided | 2020-07-30 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported with a second NPHP1 variant on the opposite allele (in trans) in a patient with isolated congenital nephrotic syndrome in the published literature; however, this individual also had variants in another gene that may have been responsible for the phenotype (Qiu et al., 2016); This variant is associated with the following publications: (PMID: 27004562) |
| Labcorp Genetics |
RCV002032780 | SCV002122741 | uncertain significance | Nephronophthisis | 2022-09-06 | 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 586 of the NPHP1 protein (p.Arg586Gln). This variant is present in population databases (rs534052463, gnomAD 0.005%). This missense change has been observed in individual(s) with congenital nephrotic syndrome (PMID: 27004562). ClinVar contains an entry for this variant (Variation ID: 1303342). 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: "Deleterious"; 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. |
| Fulgent Genetics, |
RCV002488518 | SCV002790585 | uncertain significance | Joubert syndrome with renal defect; Nephronophthisis 1; Senior-Loken syndrome 1 | 2021-09-17 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004734255 | SCV005360651 | uncertain significance | NPHP1-related disorder | 2024-08-06 | no assertion criteria provided | clinical testing | The NPHP1 c.1757G>A variant is predicted to result in the amino acid substitution p.Arg586Gln. This variant in the compound heterozygous condition along with a second variant in this gene has been reported in an individual with nephrotic syndrome, who also carried two compound heterozygous variants in LAMB2 gene (Qiu et al 2016. PubMed ID: 27004562). This variant is reported in 0.0050% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |