Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000233283 | SCV000290049 | uncertain significance | Nephronophthisis | 2022-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 459 of the NPHP4 protein (p.Thr459Lys). This variant is present in population databases (rs371819898, gnomAD 0.1%). 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: 240964). 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 not 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. |
Eurofins Ntd Llc |
RCV000728565 | SCV000856157 | uncertain significance | not provided | 2018-02-06 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002487080 | SCV002785587 | uncertain significance | Nephronophthisis 4; Senior-Loken syndrome 4 | 2022-02-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002516328 | SCV003687541 | uncertain significance | Inborn genetic diseases | 2021-07-20 | criteria provided, single submitter | clinical testing | The c.1376C>A (p.T459K) alteration is located in exon 11 (coding exon 10) of the NPHP4 gene. This alteration results from a C to A substitution at nucleotide position 1376, causing the threonine (T) at amino acid position 459 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Preventiongenetics, |
RCV003401182 | SCV004104770 | uncertain significance | NPHP4-related condition | 2022-10-06 | criteria provided, single submitter | clinical testing | The NPHP4 c.1376C>A variant is predicted to result in the amino acid substitution p.Thr459Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.082% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-5987774-G-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |