ClinVar Miner

Submissions for variant NM_152419.3(HGSNAT):c.1271dup (p.Ile425fs)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001175525 SCV001339133 pathogenic Sanfilippo syndrome 2020-03-20 criteria provided, single submitter clinical testing Variant summary: HGSNAT c.1271dupG (p.Ile425HisfsX45) 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 240376 control chromosomes (gnomAD). c.1271dupG has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IIIC (Sanfilippo Syndrome C) (Feldhammer_2009, Martins_2019). 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. 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.
Invitae RCV001383041 SCV001582050 pathogenic Mucopolysaccharidosis, MPS-III-C; Retinitis pigmentosa 73 2020-07-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile425Hisfs*45) 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 observed in individual(s) with mucopolysaccharidosis type IIIC (PMID: 19479962). Loss-of-function variants in HGSNAT are known to be pathogenic (PMID: 17033958, 19479962). For these reasons, this variant has been classified as Pathogenic.
Inherited Eye Disorders lab, UCL Institute of Ophthalmology RCV001250773 SCV001426187 pathogenic Retinitis pigmentosa 73 2020-07-01 no assertion criteria provided clinical testing

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