Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001055248 | SCV001219627 | uncertain significance | Epilepsy, familial focal, with variable foci 3 | 2024-01-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 437 of the NPRL3 protein (p.Arg437Cys). This variant is present in population databases (rs530150587, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NPRL3-related conditions. ClinVar contains an entry for this variant (Variation ID: 850957). 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 NPRL3 protein function with a negative predictive value of 80%. 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. |
Neuberg Centre For Genomic Medicine, |
RCV001055248 | SCV005042925 | uncertain significance | Epilepsy, familial focal, with variable foci 3 | criteria provided, single submitter | clinical testing | The missense c.1309C>T p.Arg437Cys variant in NPRL3 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Arg437Cys variant is reported with allele frequency of 0.004% in gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Arg437Cys in NPRL3 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Arg at position 437 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance VUS. |