Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000730347 | SCV000858076 | uncertain significance | not provided | 2018-03-19 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001070602 | SCV001235863 | uncertain significance | Nephronophthisis | 2025-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 905 of the NPHP4 protein (p.Ser905Asn). This variant is present in population databases (rs368298952, gnomAD 0.08%). 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: 594942). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt NPHP4 protein function with a negative predictive value of 80%. 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, |
RCV002499356 | SCV002797106 | uncertain significance | Nephronophthisis 4; Senior-Loken syndrome 4 | 2022-01-11 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002535153 | SCV003738135 | uncertain significance | Inborn genetic diseases | 2024-12-07 | criteria provided, single submitter | clinical testing | The c.2714G>A (p.S905N) alteration is located in exon 20 (coding exon 19) of the NPHP4 gene. This alteration results from a G to A substitution at nucleotide position 2714, causing the serine (S) at amino acid position 905 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV004535833 | SCV004116510 | uncertain significance | NPHP4-related disorder | 2022-08-23 | criteria provided, single submitter | clinical testing | The NPHP4 c.2714G>A variant is predicted to result in the amino acid substitution p.Ser905Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.080% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-5937256-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |