ClinVar Miner

Submissions for variant NM_152419.3(HGSNAT):c.607C>T (p.Arg203Ter) (rs1563366896)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000689696 SCV000817360 pathogenic Mucopolysaccharidosis, MPS-III-C; Retinitis pigmentosa 73 2019-08-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg203*) in the HGSNAT gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with mucopolysaccharidosis IIIC (PMID: 18024218). Loss-of-function variants in HGSNAT are known to be pathogenic (PMID: 17033958, 19479962). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780340 SCV000917523 pathogenic Sanfilippo syndrome 2018-04-11 criteria provided, single submitter clinical testing Variant summary: HGSNAT c.607C>T (p.Arg203X) 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 (e.g. c.1150C>T (p.Arg384X)). The variant was absent in 216360 control chromosomes in gnomAD. c.607C>T has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IIIC (Sanfilippo Syndrome C) (Ruijter 2008). Two publications reported experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Ruijter 2008, Gomez-Grau 2015). 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.

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