ClinVar Miner

Submissions for variant NM_000202.8(IDS):c.1403G>C (p.Arg468Pro)

dbSNP: rs113993946
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics, Fulgent Genetics RCV004526612 SCV005682987 likely pathogenic Mucopolysaccharidosis, MPS-II 2024-03-22 criteria provided, single submitter clinical testing
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV004526612 SCV005089555 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_Strong), 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)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526612 SCV005039728 pathogenic Mucopolysaccharidosis, MPS-II 2024-03-19 criteria provided, single submitter clinical testing Variant summary: IDS c.1403G>C (p.Arg468Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183290 control chromosomes (gnomAD). c.1403G>C has been reported in the literature in individuals affected with Mucopolysaccharidosis Type II (Hunter Syndrome; Charoenwattanasatien_2012, Ramirez-Hernanzez_2022). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, finding that the variant results in no IDS activity in transfected COS7 cells (Charoenwattanasatien_2012). Other missense variants affecting this residue have been determined to be pathogenic. The following publications have been ascertained in the context of this evaluation (PMID: 22990955, 35916809). ClinVar contains an entry for this variant (Variation ID: 92615). Based on the evidence outlined above, the variant was classified as pathogenic.
Eurofins Ntd Llc (ga) RCV000180472 SCV000232922 pathogenic not provided 2015-08-11 criteria provided, single submitter clinical testing

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