Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000667938 | SCV000792466 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2017-06-26 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001214720 | SCV001386419 | pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease, axonal type 2V | 2019-05-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu120*) in the NAGLU gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed in individuals affected with mucopolysaccharidosis type III (PMID: 27590925, 19046346). ClinVar contains an entry for this variant (Variation ID: 552642). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in NAGLU are known to be pathogenic (PMID: 9832037, 10094189, 16151907). For these reasons, this variant has been classified as Pathogenic. |
| Integrated Genetics/Laboratory Corporation of America | RCV000667938 | SCV001467864 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2020-12-04 | criteria provided, single submitter | clinical testing | Variant summary: NAGLU c.358G>T (p.Glu120X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 96200 control chromosomes (gnomAD). c.358G>T has been reported in the literature in multiple individuals affected with Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B) (Whitley_2018, Truxal_2016, Pollard_2013, Piotrowska_2008). These data indicate that the variant is very likely to be associated with disease. No enzymatic activity was found in a patient derived sample who was compound heterozygous for the variant of interest and another possible pathogenic variant (Pollard_2013). Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |