Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672379 | SCV000797478 | uncertain significance | Mucopolysaccharidosis, MPS-III-B | 2018-01-30 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001855579 | SCV002183065 | uncertain significance | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V | 2022-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 410 of the NAGLU protein (p.Phe410Ser). This variant is present in population databases (rs574688121, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of mucopolysaccharidosis type IIIB (PMID: 10094189). ClinVar contains an entry for this variant (Variation ID: 556379). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002265852 | SCV002547940 | uncertain significance | not specified | 2022-05-06 | criteria provided, single submitter | clinical testing | Variant summary: NAGLU c.1229T>C (p.Phe410Ser) results in a non-conservative amino acid change located in the Alpha-N-acetylglucosaminidase, tim-barrel domain (IPR024733) 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 1.6e-05 in 251366 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1229T>C has been reported in the literature in at least one individual affected with Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B) (Weber_1999). The report does not provide unequivocal conclusions about association of the variant with Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |