Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001244521 | SCV001417747 | uncertain significance | Nephronophthisis | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with serine at codon 1294 of the NPHP4 protein (p.Arg1294Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is present in population databases (rs367814493, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. 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: "Tolerated"; PolyPhen-2: "Possibly 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, |
RCV002491819 | SCV002777886 | uncertain significance | Nephronophthisis 4; Senior-Loken syndrome 4 | 2022-04-11 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002568592 | SCV003757561 | uncertain significance | Inborn genetic diseases | 2022-08-04 | criteria provided, single submitter | clinical testing | The c.3882G>T (p.R1294S) alteration is located in exon 28 (coding exon 27) of the NPHP4 gene. This alteration results from a G to T substitution at nucleotide position 3882, causing the arginine (R) at amino acid position 1294 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |