ClinVar Miner

Submissions for variant NM_000202.8(IDS):c.1265G>A (p.Cys422Tyr)

dbSNP: rs886044835
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000374453 SCV000337656 likely pathogenic not provided 2015-11-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000811810 SCV000952097 pathogenic Mucopolysaccharidosis, MPS-II 2018-08-17 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 422 of the IDS protein (p.Cys422Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant has been observed in individuals affected with mucopolysaccharidosis II (PMID: 26762690, 27246110, 24125893). ClinVar contains an entry for this variant (Variation ID: 284860). For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the p.Cys422 amino acid residue in IDS have been observed in affected individuals (PMID: 26762690, 27246110, 24125893, 11683780, 1303211, 28077157). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0").
Genome-Nilou Lab RCV000811810 SCV002014471 likely pathogenic Mucopolysaccharidosis, MPS-II 2021-09-05 criteria provided, single submitter clinical testing
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000811810 SCV005089495 pathogenic Mucopolysaccharidosis, MPS-II 2024-06-07 criteria provided, single submitter literature only In vitro or in vivo functional studies supportive of a damaging effect (PS3_Moderate), Prevalence of the variant significantly increased in affected individuals compared with controls (PS4_Supporting), Located in a mutational hot spot and/or critical functional domain (PM1_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_Strong)

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.