ClinVar Miner

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

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
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
Fulgent Genetics,Fulgent Genetics RCV000409562 SCV000893482 pathogenic Mucopolysaccharidosis, MPS-III-A 2018-10-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America 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.
Invitae RCV000409562 SCV000937104 pathogenic Mucopolysaccharidosis, MPS-III-A 2018-08-14 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.