ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.1298G>A (p.Arg433Gln) (rs104894641)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000790770 SCV000232481 pathogenic not provided 2013-12-03 criteria provided, single submitter clinical testing
Counsyl RCV000005416 SCV000789552 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2017-02-09 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000005416 SCV000918204 pathogenic Mucopolysaccharidosis, MPS-III-A 2017-09-11 criteria provided, single submitter clinical testing Variant summary: The SGSH c.1298G>A (p.Arg433Gln) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 1/120022 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic SGSH variant (0.0032275). The variant has been reported in numerous affected individuals in the literature in both homozygous and compound heterozygous states. Patient fibroblasts as well as transfected cells showed low to non-detectable enzyme activity (Montfort_2004). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000005416 SCV001394068 pathogenic Mucopolysaccharidosis, MPS-III-A 2019-07-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 433 of the SGSH protein (p.Arg433Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs104894641, ExAC 0.002%). This variant has been observed in individual(s) with Sanfilippo syndrome A (PMID: 11343308, 12702166, 30593151). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 5109). This variant has been reported to affect SGSH protein function (PMID: 15542396). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Arg433 amino acid residue in SGSH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11182930, 15542396, 29023963). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000005416 SCV000025598 pathogenic Mucopolysaccharidosis, MPS-III-A 2003-04-01 no assertion criteria provided literature only

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.