Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001376687 | SCV003445272 | pathogenic | Mucopolysaccharidosis, MPS-II | 2021-12-30 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1065825). This missense change has been observed in individual(s) with mucopolysaccharidosis II (PMID: 9762601, 12572848, 27146977, 30639582). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 231 of the IDS protein (p.Pro231Leu). 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. For these reasons, this variant has been classified as Pathogenic. |
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV001376687 | SCV005089187 | likely 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), 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) |
Pediatrics, |
RCV001376687 | SCV001573772 | affects | Mucopolysaccharidosis, MPS-II | 2014-04-03 | no assertion criteria provided | research | The change c.692C>T, (p.P231L) was found to be a missense variant, where the cyclic nonpolar neutral amino acid Proline at 231 position was substituted by aliphatic nonpolar neutral amino acid Leucine. It was detected in the hemizygous condition in one case with attenuated phenotype from Delhi, India. |