Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Integrated 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 | 2019-09-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 234 of the NAGLU protein (p.Arg234Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs104894601, ExAC 0.02%). This variant has been observed in numerous individuals and families affected with NAGLU-related conditions (PMID: 9832037, 30070758, 11286389, 18218046, 23380547). ClinVar contains an entry for this variant (Variation ID: 1572). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000001638 | SCV000021794 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2008-03-01 | no assertion criteria provided | literature only |