Submissions for variant NM_000263.4(NAGLU):c.2045T>G (p.Leu682Arg)

dbSNP: rs2092930339

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Revvity Omics, Revvity	RCV001784706	SCV002018197	pathogenic	not provided	2021-02-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001885164	SCV002187037	pathogenic	Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V	2024-02-24	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 682 of the NAGLU protein (p.Leu682Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive mucopolysaccharidosis type IIIB (MPS IIIB) (PMID: 9443878, 11793481, 33747789). ClinVar contains an entry for this variant (Variation ID: 1323323). 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 NAGLU protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects NAGLU function (PMID: 9443878). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV001784706	SCV004704336	likely pathogenic	not provided	2024-01-01	criteria provided, single submitter	clinical testing	NAGLU: PM2, PM3, PP4, PS3:Supporting
Fulgent Genetics, Fulgent Genetics	RCV001885164	SCV005646097	likely pathogenic	Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V	2024-03-05	criteria provided, single submitter	clinical testing