Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271919 | SCV002556193 | likely pathogenic | Mucopolysaccharidosis, MPS-II | 2022-06-27 | criteria provided, single submitter | clinical testing | Variant summary: IDS c.1400C>G (p.Pro467Arg) 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). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.1400C>G, has been reported in the literature in at-least one individual affected with Mucopolysaccharidosis (Pollard_2012), in whom the enzyme deficiency has been confirmed by the authors. In addition, another missense change affecting the same residue (c.1400C>T (p.P467L)) is also reported in affected individual(s) (HGMD), and is reported to result in an almost completely absent enzyme activity in in vitro functional studies (PMID 31877959). Furthermore, several missense variants affecting surrounding amino acids (e.g. S464R, Q465P, R468Q/G/L/P/W, P469A/R/H/L, D471H) are reported in affected individuals (HGMD), indicating a functional importance for this protein region. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV002271919 | SCV005089549 | pathogenic | Mucopolysaccharidosis, MPS-II | 2024-06-07 | criteria provided, single submitter | literature only | Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Missense change at the same amino acid residue as a pathogenic variant (PM5_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) |