Submissions for variant NM_016373.4(WWOX):c.898A>G (p.Asn300Asp)

gnomAD frequency: 0.00012  dbSNP: rs374541202

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000229679	SCV000290228	uncertain significance	Developmental and epileptic encephalopathy, 1; Autosomal recessive spinocerebellar ataxia 12	2025-02-03	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine with aspartic acid at codon 300 of the WWOX protein (p.Asn300Asp). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in population databases (rs374541202, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with WWOX-related conditions. ClinVar contains an entry for this variant (Variation ID: 241107). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt WWOX 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.
Genetic Services Laboratory, University of Chicago	RCV000502667	SCV000597998	uncertain significance	not specified	2016-08-11	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV003137849	SCV003823811	uncertain significance	not provided	2020-04-17	criteria provided, single submitter	clinical testing
GeneDx	RCV003137849	SCV004021573	uncertain significance	not provided	2023-07-18	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; This variant is associated with the following publications: (PMID: 25411445)
Mayo Clinic Laboratories, Mayo Clinic	RCV003137849	SCV004227610	uncertain significance	not provided	2022-08-04	criteria provided, single submitter	clinical testing	PP3, PM2
CeGaT Center for Human Genetics Tuebingen	RCV003137849	SCV005050946	uncertain significance	not provided	2024-05-01	criteria provided, single submitter	clinical testing	WWOX: PM2, PP3