ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.364G>A (p.Gly122Arg) (rs761607612)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000612947 SCV000745251 pathogenic Mucopolysaccharidosis, MPS-III-A 2015-09-21 criteria provided, single submitter clinical testing
Counsyl RCV000612947 SCV000797367 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2018-01-24 criteria provided, single submitter clinical testing
Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padova RCV000612947 SCV000929894 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2019-01-01 criteria provided, single submitter literature only PS3: Low in vitro enzymatic activity. PM2: Very low frequency in ExAc
Invitae RCV000612947 SCV000954450 pathogenic Mucopolysaccharidosis, MPS-III-A 2020-10-09 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 122 of the SGSH protein (p.Gly122Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs761607612, ExAC 0.01%). This variant has been observed to be homozygous or in combination with another SGSH variant in individuals affected with mucopolysaccharidosis (PMID: 9401012, 21061399, 27590925, 22976768, 9554748, 11182930, Invitae). ClinVar contains an entry for this variant (Variation ID: 518269). Experimental studies have shown that this missense change abrogates SGSH enzyme activity (PMID: 10727844). This variant disrupts the p.Arg122 amino acid residue in SGSH. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 24875751), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Centre for Inherited Metabolic Diseases, Karolinska University Hospital RCV000612947 SCV001548178 pathogenic Mucopolysaccharidosis, MPS-III-A 2021-03-25 criteria provided, single submitter clinical testing
GeneDx RCV001539080 SCV001756817 pathogenic not provided 2021-08-05 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect on enzyme activity (Esposito et al., 2000); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 9401012, 9554748, 11182930, 11668611, 21204211, 22002444, 24875751, 30809705, 10727844, 22976768, 27590925, 21061399, 25557439, 25807448, 24816101)
Nilou-Genome Lab RCV000612947 SCV002045505 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2021-11-07 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000612947 SCV000733743 pathogenic Mucopolysaccharidosis, MPS-III-A no assertion criteria provided clinical testing

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