Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000078459 | SCV000110315 | pathogenic | not provided | 2012-08-09 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000664563 | SCV000788550 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2017-12-29 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000664563 | SCV002500655 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2022-03-26 | criteria provided, single submitter | clinical testing | Variant summary: NAGLU c.503G>A (p.Trp168X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251134 control chromosomes. c.503G>A has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B) (example, Coll_2001, Mangas_2008). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV002514378 | SCV003441860 | pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V | 2022-11-01 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 92695). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type III (PMID: 11286389, 18218046). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp168*) in the NAGLU gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NAGLU are known to be pathogenic (PMID: 9832037, 10094189, 16151907). |