ClinVar Miner

Submissions for variant NM_000263.4(NAGLU):c.1876C>T (p.Arg626Ter) (rs104894591)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000153533 SCV000203061 pathogenic not provided 2013-12-19 criteria provided, single submitter clinical testing
Counsyl RCV000001627 SCV000789321 pathogenic Mucopolysaccharidosis, MPS-III-B 2017-01-25 criteria provided, single submitter clinical testing
Invitae RCV000802847 SCV000942693 pathogenic Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease, axonal type 2V 2019-06-19 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the NAGLU gene (p.Arg626*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 118 amino acids of the NAGLU protein. This variant is present in population databases (rs104894591, ExAC 0.02%). This variant has been observed in several individuals affected with mucopolysaccharidosis (PMID: 9832037, 8650226, 10094189). ClinVar contains an entry for this variant (Variation ID: 1561). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000001627 SCV001362138 pathogenic Mucopolysaccharidosis, MPS-III-B 2019-11-11 criteria provided, single submitter clinical testing Variant summary: NAGLU c.1876C>T (p.Arg626X) 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 allele was found at a frequency of 2.2e-05 in 229530 control chromosomes. c.1876C>T has been reported in the literature in multiple individuals affected with Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B) (Beesley_1998, Weber_1999, Zhao_1996, Zhao_1998). These data indicate that the variant is very likely to be associated with disease. No experimental evidence demonstrating an impact on protein function was ascertained. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000001627 SCV000021783 pathogenic Mucopolysaccharidosis, MPS-III-B 1996-06-11 no assertion criteria provided literature only

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