ClinVar Miner

Submissions for variant NM_000263.4(NAGLU):c.358G>T (p.Glu120Ter)

dbSNP: rs1445294968
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Total submissions: 4
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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
Labcorp Genetics (formerly Invitae), Labcorp RCV001214720 SCV001386419 pathogenic Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V 2024-05-15 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. 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 III (PMID: 19046346, 27590925, 29661560). ClinVar contains an entry for this variant (Variation ID: 552642). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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.
Natera, Inc. RCV000667938 SCV002093250 pathogenic Mucopolysaccharidosis, MPS-III-B 2021-06-18 no assertion criteria provided clinical testing

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