Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000318135 | SCV000342109 | uncertain significance | not provided | 2018-03-02 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001041243 | SCV001204846 | uncertain significance | Nephronophthisis | 2022-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 857 of the NPHP4 protein (p.Arg857Cys). This variant is present in population databases (rs372688518, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. ClinVar contains an entry for this variant (Variation ID: 288104). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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, |
RCV002487252 | SCV002786981 | uncertain significance | Nephronophthisis 4; Senior-Loken syndrome 4 | 2022-03-03 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004021241 | SCV004990991 | uncertain significance | Inborn genetic diseases | 2023-11-06 | criteria provided, single submitter | clinical testing | The c.2569C>T (p.R857C) alteration is located in exon 19 (coding exon 18) of the NPHP4 gene. This alteration results from a C to T substitution at nucleotide position 2569, causing the arginine (R) at amino acid position 857 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Prevention |
RCV004535408 | SCV004755536 | uncertain significance | NPHP4-related disorder | 2024-08-24 | no assertion criteria provided | clinical testing | The NPHP4 c.2569C>T variant is predicted to result in the amino acid substitution p.Arg857Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0070% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |