Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001844476 | SCV002103425 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2022-02-08 | criteria provided, single submitter | clinical testing | Variant summary: NAGLU c.410_413delCGCA (p.Thr137LysfsX17) 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 251458 control chromosomes. c.410_413delCGCA has been reported in the literature as a compound heterozygous genotype or with a second allele not specified in at-least two individuals from families affected with Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B) (example, Beesley_2005). To our knowledge, no variant specific experimental evidence demonstrating an impact on protein function has been reported although the reported patients with this variant displayed classic features of disease confirmed by quantitative analysis of urinary glycosaminoglycan (GAGs) and enzyme assay for NAGLU (alpha-N-acetylglucosaminidase) (example, Beesley_2005). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV005225522 | SCV005863386 | pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V | 2024-09-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr137Lysfs*17) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type IIIB (PMID: 16151907). This variant is also known as 407-410del4. ClinVar contains an entry for this variant (Variation ID: 1343458). For these reasons, this variant has been classified as Pathogenic. |