Submissions for variant NM_000263.4(NAGLU):c.2020C>T (p.Arg674Cys)

gnomAD frequency: 0.00002  dbSNP: rs763299645

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000668435	SCV000793035	likely pathogenic	Mucopolysaccharidosis, MPS-III-B	2017-07-27	criteria provided, single submitter	clinical testing
Invitae	RCV001248721	SCV001422227	pathogenic	Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V	2024-01-01	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 674 of the NAGLU protein (p.Arg674Cys). This variant is present in population databases (rs763299645, gnomAD 0.007%). This missense change has been observed in individual(s) with mucopolysaccharidosis type IIIB (PMID: 9443875, 10094189). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 553061). 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%. This variant disrupts the p.Arg674 amino acid residue in NAGLU. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8650226, 9443875, 9950362, 20852935). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino	RCV001838091	SCV002098101	likely pathogenic	Tip-toe gait	2021-11-30	criteria provided, single submitter	clinical testing
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV000668435	SCV002822859	likely pathogenic	Mucopolysaccharidosis, MPS-III-B		criteria provided, single submitter	clinical testing	The homozygous missense variation in exon 6 of NAGLU gene that results in the amino acid substitution to cysteine for arginine at codon of 674 was detected. The variant c.2020C>T (p.Arg674Cys) has not been reported in 1000 genome and has a MAF of 0.0016% in the gnomAD database. The insilico prediction of the variant is dIsease causing by MutationTaster , LRT, SIFT, PROVEAN and DANN.
Revvity Omics, Revvity	RCV003140063	SCV003825873	pathogenic	not provided	2021-12-20	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000668435	SCV002093281	pathogenic	Mucopolysaccharidosis, MPS-III-B	2021-09-14	no assertion criteria provided	clinical testing
Molecular Biology Laboratory, Department of Zoology, Quaid-i-azam University	RCV000668435	SCV004012870	pathogenic	Mucopolysaccharidosis, MPS-III-B		no assertion criteria provided	research