Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV004597029 | SCV005089392 | likely 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 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_Moderate) |
Labcorp Genetics |
RCV004597029 | SCV005839504 | uncertain significance | Mucopolysaccharidosis, MPS-II | 2025-01-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 344 of the IDS protein (p.Glu344Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with mucopolysaccharidosis (PMID: 24125893, 24875751). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt IDS protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |