ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.697C>T (p.Arg233Ter) (rs374621913)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409562 SCV000486121 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2016-11-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588098 SCV000695959 pathogenic Sanfilippo syndrome 2017-07-17 criteria provided, single submitter clinical testing Variant summary: The c.697C>T (p.Arg233*) variant in SGSH gene is a nonsense change that results in the loss of the ~54% of the length of the protein (270 aa). This change is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay, which was proven by RNA and protein expression studies (Muschol, 2004). The variant is present in the large control population dataset of ExAC at a low frequency 1.1e-05 (1/90902 chrs tested). This frequency does not exceed the maximal expected frequency of a pathogenic allele (0.0032 in this gene. The variant of interest has been reported in numerous affected individual homozygously or in compound heterozygous state. In addition, the variant is cited as Pathogenic by multiple reputable database/diagnostic centers. Taking together, the variant was classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000409562 SCV000893482 pathogenic Mucopolysaccharidosis, MPS-III-A 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000409562 SCV000937104 pathogenic Mucopolysaccharidosis, MPS-III-A 2020-10-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg233*) in the SGSH gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs374621913, ExAC 0.002%). This variant has been observed in combination with another SGSH variant in an individual, affected with mucopolysaccharidosis type III (PMID: 15146460). ClinVar contains an entry for this variant (Variation ID: 370732). Loss-of-function variants in SGSH are known to be pathogenic (PMID: 11182930, 21204211, 22976768). For these reasons, this variant has been classified as Pathogenic.
Nilou-Genome Lab RCV000409562 SCV002045497 pathogenic Mucopolysaccharidosis, MPS-III-A 2021-11-07 criteria provided, single submitter clinical testing
Natera, Inc. RCV000409562 SCV001453821 pathogenic Mucopolysaccharidosis, MPS-III-A 2020-09-16 no assertion criteria provided clinical testing

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