ClinVar Miner

Submissions for variant NM_000202.8(IDS):c.998C>G (p.Ser333Trp)

dbSNP: rs104894853
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001949645 SCV002238415 pathogenic Mucopolysaccharidosis, MPS-II 2022-05-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser333 amino acid residue in IDS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1639384, 28543354, 30639582; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 IDS protein function. This missense change has been observed in individual(s) with mucopolysaccharidosis type II (PMID: 17391447). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 333 of the IDS protein (p.Ser333Trp).
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV001949645 SCV005089335 likely pathogenic Mucopolysaccharidosis, MPS-II 2024-06-07 criteria provided, single submitter literature only Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Missense change at the same amino acid residue as a pathogenic variant (PM5_Moderate), Missense variant in a gene with a low rate of benign missense variation (PP2_Supporting), Multiple lines of computational evidence support a deleterious effect (PP3_Supporting), Patient’s phenotype or family history highly specific for the disease (PP4_Moderate)

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