Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000001638 | SCV000919840 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2017-11-20 | criteria provided, single submitter | clinical testing | Variant summary: The NAGLU c.700C>T (p.Arg234Cys) variant located in the alpha-n-acetylglucosaminidase, tim-barrel domain (via InterPro) involves the alteration of a conserved nucleotide and 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 10/276804 control chromosomes (gnomAD and publication controls) at a frequency of 0.0000361, which does not exceed the estimated maximal expected allele frequency of a pathogenic NAGLU variant (0.0025). Multiple publications have cited the variant in compound heterozygote and homozygote MPS IIIB pts and found NAGLU activity to be significantly decreased (Mangas_2008). In addition, a reputable database, OMIM classifies the variant as "pathogenic." Taken together, this variant is classified as pathogenic. |
| Mendelics | RCV000001638 | SCV001140445 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001203422 | SCV001374588 | pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V | 2023-10-20 | 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 234 of the NAGLU protein (p.Arg234Cys). This variant is present in population databases (rs104894601, gnomAD 0.02%). This missense change has been observed in individual(s) with NAGLU-related conditions (PMID: 9832037, 11286389, 18218046, 23380547, 30070758). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1572). 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. For these reasons, this variant has been classified as Pathogenic. |
| DASA | RCV000001638 | SCV002318971 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2022-03-25 | criteria provided, single submitter | clinical testing | The c.700C>T;p.(Arg234Cys) missense change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 1572; PMID: 9832037; PMID: 30070758; PMID: 11286389; PMID: 18218046; PMID: 23380547) -PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain (NAGLU) - PM1. The variant is present at low allele frequencies population databases (rs104894601 – gnomAD 0.0003188%; ABraOM no frequency - http://abraom.ib.usp.br.) - PM2_supporting. The p.(Arg234Cys) was detected in trans with a pathogenic variant (PMID: 11286389; PMID: 30070758) - PM3. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic |
| OMIM | RCV000001638 | SCV000021794 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2008-03-01 | no assertion criteria provided | literature only | |
| Natera, |
RCV000001638 | SCV001463384 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2020-09-16 | no assertion criteria provided | clinical testing |