ClinVar Miner

Submissions for variant NM_000202.8(IDS):c.1265G>A (p.Cys422Tyr) (rs886044835)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000374453 SCV000337656 likely pathogenic not provided 2015-11-10 criteria provided, single submitter clinical testing
Invitae RCV000811810 SCV000952097 pathogenic Mucopolysaccharidosis, MPS-II 2018-08-27 criteria provided, single submitter clinical testing 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 is not present in population databases (ExAC no frequency). 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). 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"). 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. For these reasons, this variant has been classified as Pathogenic.

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