Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001248000 | SCV001421459 | uncertain significance | Nephronophthisis | 2022-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 924 of the NPHP4 protein (p.Leu924Val). This variant is present in population databases (rs770984804, gnomAD 0.002%). 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: 972063). 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. 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, |
RCV002484391 | SCV002791655 | uncertain significance | Nephronophthisis 4; Senior-Loken syndrome 4 | 2022-04-22 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004034913 | SCV004990997 | uncertain significance | Inborn genetic diseases | 2024-01-30 | criteria provided, single submitter | clinical testing | The c.2770C>G (p.L924V) alteration is located in exon 20 (coding exon 19) of the NPHP4 gene. This alteration results from a C to G substitution at nucleotide position 2770, causing the leucine (L) at amino acid position 924 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |