Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000674403 | SCV000799732 | uncertain significance | Mucopolysaccharidosis, MPS-III-B | 2018-05-03 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193369 | SCV001362137 | uncertain significance | not specified | 2019-10-04 | criteria provided, single submitter | clinical testing | Variant summary: NAGLU c.1772T>C (p.Leu591Pro) results in a non-conservative amino acid change located in the Alpha-N-acetylglucosaminidase, C-terminal of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.2e-06 in 242902 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1772T>C has been reported in the literature in a compound heterozygote individual affected with a severe form of Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B)(Beesley_1998). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV001855608 | SCV002116927 | pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 591 of the NAGLU protein (p.Leu591Pro). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with clinical features of mucopolysaccharidosis type IIIB (PMID: 9832037; Invitae). 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: 558175). 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%. For these reasons, this variant has been classified as Pathogenic. |
Natera, |
RCV000674403 | SCV002093280 | uncertain significance | Mucopolysaccharidosis, MPS-III-B | 2020-02-03 | no assertion criteria provided | clinical testing |