Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001042629 | SCV001206325 | uncertain significance | Nephronophthisis | 2022-06-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 555 of the NPHP4 protein (p.Gln555Glu). This variant is not present in population databases (gnomAD no frequency). 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: 840593). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
Ambry Genetics | RCV003307827 | SCV003988957 | uncertain significance | Inborn genetic diseases | 2023-06-06 | criteria provided, single submitter | clinical testing | The c.1663C>G (p.Q555E) alteration is located in exon 14 (coding exon 13) of the NPHP4 gene. This alteration results from a C to G substitution at nucleotide position 1663, causing the glutamine (Q) at amino acid position 555 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |