Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004597119 | SCV006072391 | pathogenic | Mucopolysaccharidosis, MPS-II | 2025-03-28 | criteria provided, single submitter | clinical testing | Variant summary: IDS c.1295G>A (p.Cys432Tyr) 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 181991 control chromosomes. c.1295G>A has been reported in the literature in multiple individuals affected with Mucopolysaccharidosis Type II (Hunter Syndrome) (e.g., Karsten_1998, Christiakov_2014, Semyachkina_2021, Gragniello_2022, Zhong_2023, Zabihi_2024). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 24780617, 35782619, 9921913, 33676511, 38425718, 36945845). ClinVar contains an entry for this variant (Variation ID: 3256020). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV004597119 | SCV005089516 | pathogenic | Mucopolysaccharidosis, MPS-II | 2024-06-07 | criteria provided, single submitter | literature only | 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) |