Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001216444 | SCV001388241 | uncertain significance | Nephronophthisis | 2023-08-04 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NPHP4 protein function. ClinVar contains an entry for this variant (Variation ID: 945735). This variant is present in population databases (rs373603595, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 914 of the NPHP4 protein (p.Arg914Cys). |
| Fulgent Genetics, |
RCV002491669 | SCV002797576 | uncertain significance | Nephronophthisis 4; Senior-Loken syndrome 4 | 2022-04-14 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002561895 | SCV003714711 | uncertain significance | Inborn genetic diseases | 2022-08-03 | criteria provided, single submitter | clinical testing | The c.2740C>T (p.R914C) alteration is located in exon 20 (coding exon 19) of the NPHP4 gene. This alteration results from a C to T substitution at nucleotide position 2740, causing the arginine (R) at amino acid position 914 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |