Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000210561 | SCV000262839 | likely pathogenic | Inborn genetic diseases | 2013-12-09 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002517434 | SCV003525453 | pathogenic | Nephronophthisis | 2022-03-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 NPHP3 protein function. ClinVar contains an entry for this variant (Variation ID: 224989). This missense change has been observed in individual(s) with clinical features of nephronophthisis (PMID: 25356970). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 640 of the NPHP3 protein (p.Asp640Glu). |