Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000597836 | SCV000707152 | uncertain significance | not provided | 2018-07-06 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000638099 | SCV000759579 | uncertain significance | Nephronophthisis | 2022-10-31 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1098 of the NPHP4 protein (p.Ala1098Thr). This variant is present in population databases (rs41280798, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with nephronophthisis and focal segmental glomerulosclerosis (PMID: 15776426, 26346198). ClinVar contains an entry for this variant (Variation ID: 500975). 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. Experimental studies have shown that this missense change does not substantially affect NPHP4 function (PMID: 21546380). 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, |
RCV000765245 | SCV000896492 | uncertain significance | Nephronophthisis 4; Senior-Loken syndrome 4 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001096629 | SCV001252853 | likely benign | Nephronophthisis 4 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |