ClinVar Miner

Submissions for variant NM_000202.8(IDS):c.262C>T (p.Arg88Cys) (rs398123249)

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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 RCV000790676 SCV000228818 pathogenic not provided 2013-01-09 criteria provided, single submitter clinical testing
Invitae RCV000177014 SCV000628121 pathogenic Mucopolysaccharidosis, MPS-II 2017-08-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 88 of the IDS protein (p.Arg88Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in several individuals affected with mucopolysaccharidosis type II (PMID: 7814022, 8940265 , 9950361 , 15614569, 17063374, 22990955, 24125893, 26762690). ClinVar contains an entry for this variant (Variation ID: 92618). A different missense substitution at this codon (p.Arg88His) has been determined to be pathogenic (PMID: 9921913, 9660053, 10215411, 10838181, 24515576). This suggests that the arginine residue is critical for IDS protein function and that other missense substitutions at this position may also be pathogenic. Experimental studies have shown that this missense change affects IDS post-translational modification and results in a protein with an almost undetectable enzymatic activity (PMID: 15614569, 22990955). For these reasons, this variant has been classified as Pathogenic.

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