Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
EGL Genetic Diagnostics, |
RCV000726607 | SCV000345803 | uncertain significance | not provided | 2016-09-01 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV000283485 | SCV000441157 | uncertain significance | Nephronophthisis | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV000343202 | SCV000441158 | uncertain significance | Renal-hepatic-pancreatic dysplasia 1 | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV000404760 | SCV000441159 | uncertain significance | Meckel-Gruber syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000726607 | SCV000590321 | uncertain significance | not provided | 2017-06-13 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the NPHP3 gene. The G78V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G78V variant is observed in 1/8252 (0.01%) alleles from individuals of East Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G78V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Glycine are tolerated across species. However, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV000283485 | SCV000831174 | uncertain significance | Nephronophthisis | 2019-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with valine at codon 78 of the NPHP3 protein (p.Gly78Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs202142404, ExAC 0.01%). This variant has not been reported in the literature in individuals with NPHP3-related disease. ClinVar contains an entry for this variant (Variation ID: 291105). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |