Submissions for variant NM_001077350.3(NPRL3):c.275G>A (p.Arg92Gln)

gnomAD frequency: 0.00007  dbSNP: rs367729589

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000706116	SCV000835148	uncertain significance	Epilepsy, familial focal, with variable foci 3	2024-01-27	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 92 of the NPRL3 protein (p.Arg92Gln). 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 missense change has been observed in individual(s) with familial cortical dysplasia and/or frontal lobe epilepsy (PMID: 26285051, 26505888). ClinVar contains an entry for this variant (Variation ID: 582124). 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 NPRL3 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect NPRL3 function (PMID: 31639411). 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.
Revvity Omics, Revvity	RCV000706116	SCV003814139	uncertain significance	Epilepsy, familial focal, with variable foci 3	2022-07-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003222117	SCV003917436	uncertain significance	not provided	2023-05-01	criteria provided, single submitter	clinical testing