Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000728100 | SCV000855633 | uncertain significance | not provided | 2017-07-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001366737 | SCV001563051 | uncertain significance | Nephronophthisis | 2022-04-15 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 413 of the NPHP4 protein (p.Ile413Thr). This variant is present in population databases (rs373614448, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. 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: 593141). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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, |
RCV002485854 | SCV002779622 | uncertain significance | Nephronophthisis 4; Senior-Loken syndrome 4 | 2022-04-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002535057 | SCV003537087 | uncertain significance | Inborn genetic diseases | 2021-10-13 | criteria provided, single submitter | clinical testing | The c.1238T>C (p.I413T) alteration is located in exon 10 (coding exon 9) of the NPHP4 gene. This alteration results from a T to C substitution at nucleotide position 1238, causing the isoleucine (I) at amino acid position 413 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |