ClinVar Miner

Submissions for variant NM_000202.8(IDS):c.469C>T (p.Pro157Ser)

dbSNP: rs864622774
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
IIFP, CONICET-UNLP RCV000205861 SCV000262523 pathogenic Mucopolysaccharidosis, MPS-II 2013-06-24 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV000205861 SCV002138548 uncertain significance Mucopolysaccharidosis, MPS-II 2024-08-30 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 157 of the IDS protein (p.Pro157Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Hunter syndrome (PMID: 27896113). ClinVar contains an entry for this variant (Variation ID: 221209). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on IDS protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV002247637 SCV002517201 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000205861 SCV005089089 likely pathogenic Mucopolysaccharidosis, MPS-II 2024-06-07 criteria provided, single submitter literature only Prevalence of the variant significantly increased in affected individuals compared with controls (PS4_Moderate), Absent from controls (or at low frequency) in gnomAD database (PM2_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)
3billion RCV000205861 SCV005905774 uncertain significance Mucopolysaccharidosis, MPS-II 2023-11-15 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Missense variant In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.77 (>=0.6, sensitivity 0.68 and specificity 0.92)]. Same nucleotide change resulting in same amino acid change (PMID: 27896113) and a different missense change at the same codon (p.Pro157His / PMID: 35571021) have been previously reported to be associated with IDS related disorder. However the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline.

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