Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000819855 | SCV000960538 | uncertain significance | Epilepsy, familial focal, with variable foci 3 | 2023-05-09 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 662248). This variant has not been reported in the literature in individuals affected with NPRL3-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 401 of the NPRL3 protein (p.Arg401Gln). 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. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. |
| Gene |
RCV004768702 | SCV005379267 | uncertain significance | not provided | 2023-11-08 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. |
| Ambry Genetics | RCV004958163 | SCV005464428 | uncertain significance | Inborn genetic diseases | 2024-06-25 | criteria provided, single submitter | clinical testing | The c.1202G>A (p.R401Q) alteration is located in exon 12 (coding exon 11) of the NPRL3 gene. This alteration results from a G to A substitution at nucleotide position 1202, causing the arginine (R) at amino acid position 401 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |