ClinVar Miner

Submissions for variant NM_000263.4(NAGLU):c.1900G>A (p.Glu634Lys) (rs147036053)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000779220 SCV000915763 uncertain significance Mucopolysaccharidosis, MPS-III-B 2018-12-07 criteria provided, single submitter clinical testing The NAGLU c.1900G>A (p.Glu634Lys) missense variant has been reported in two studies and found in three individuals with MPS type IIIB from two unrelated families, all in a compound heterozygous state (Valstar et al. 2010; Truxal et al. 2016). In the sibling pair, this variant was associated with an attenuated phenotype of MPS IIIB with a slower progression of disease (Valstar et al. 2010). Control data are unavailable for this variant, which is reported at a frequency of 0.000033 in the European (non-Finnish) population of the Genome Aggregation Database. Though functional studies were not available, one study demonstrated deficient alpha-N-acetyl glucosaminidase (NAGLU) enzyme activity in cultured fibroblasts from the affected sibling pair (Meijer et al. 2016). Based on the limited evidence, the p.Glu634Lys variant is classified as a variant of unknown significance but suspicious for pathogenicity for mucopolysaccharidosis type III. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000806351 SCV000946343 likely pathogenic Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease, axonal type 2V 2018-12-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 634 of the NAGLU protein (p.Glu634Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another NAGLU variant in individuals affected with mucopolysaccharidosis type III (PMID: 20852935, 27590925, Invitae). 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 C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.