Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003509089 | SCV004299018 | pathogenic | Mucopolysaccharidosis, MPS-II | 2022-10-21 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IDS protein function. This missense change has been observed in individual(s) with mucopolysaccharidosis type II (PMID: 8940265, 33676511). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 184 of the IDS protein (p.Cys184Phe). |
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV003509089 | SCV005089122 | pathogenic | Mucopolysaccharidosis, MPS-II | 2024-06-07 | criteria provided, single submitter | literature only | 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) |