Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001940605 | SCV002194618 | uncertain significance | Nephronophthisis | 2022-10-25 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1419186). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. This variant is present in population databases (rs769488870, gnomAD 0.006%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1293 of the NPHP4 protein (p.Val1293Met). |
Ambry Genetics | RCV002557803 | SCV003622230 | uncertain significance | Inborn genetic diseases | 2022-05-04 | criteria provided, single submitter | clinical testing | The c.3877G>A (p.V1293M) alteration is located in exon 28 (coding exon 27) of the NPHP4 gene. This alteration results from a G to A substitution at nucleotide position 3877, causing the valine (V) at amino acid position 1293 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |