Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001931098 | SCV002196632 | uncertain significance | Nephronophthisis | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 304 of the NPHP4 protein (p.Val304Ile). This variant is present in population databases (rs571395593, gnomAD 0.008%). 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: 1419053). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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, |
RCV002507046 | SCV002802052 | uncertain significance | Nephronophthisis 4; Senior-Loken syndrome 4 | 2022-05-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003348630 | SCV004068471 | uncertain significance | Inborn genetic diseases | 2023-06-30 | criteria provided, single submitter | clinical testing | The c.910G>A (p.V304I) alteration is located in exon 8 (coding exon 7) of the NPHP4 gene. This alteration results from a G to A substitution at nucleotide position 910, causing the valine (V) at amino acid position 304 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |