ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.268G>A (p.Gly90Arg)

gnomAD frequency: 0.00001  dbSNP: rs774010006
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665315 SCV000789415 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2017-02-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000665315 SCV001362833 pathogenic Mucopolysaccharidosis, MPS-III-A 2019-11-15 criteria provided, single submitter clinical testing Variant summary: SGSH c.268G>A (p.Gly90Arg) results in a non-conservative amino acid change located in the Sulfatase, N-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 248612 control chromosomes (gnomAD). c.268G>A has been reported in the literature in multiple individuals affected with Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome A)(Bunge_1997, Sun_2011, Heron_2011, Chistiakov_2014). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000665315 SCV001372574 pathogenic Mucopolysaccharidosis, MPS-III-A 2023-09-08 criteria provided, single submitter clinical testing This variant is present in population databases (rs774010006, gnomAD 0.006%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 90 of the SGSH protein (p.Gly90Arg). This missense change has been observed in individual(s) with clinical features of SGSH-related conditions (PMID: 21204211, 21455105, 24875751). ClinVar contains an entry for this variant (Variation ID: 550542). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SGSH protein function. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000665315 SCV002045506 pathogenic Mucopolysaccharidosis, MPS-III-A 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV000665315 SCV004201097 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2023-09-09 criteria provided, single submitter clinical testing

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