Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001852648 | SCV002243338 | pathogenic | Mucolipidosis type II; Pseudo-Hurler polydystrophy | 2022-08-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GNPTAB function (PMID: 25505245, 25788519). 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 GNPTAB protein function. ClinVar contains an entry for this variant (Variation ID: 39026). This missense change has been observed in individual(s) with clinical features of mucolipdosis III alpha/beta (PMID: 19659762, 23566849, 28649523). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs281864973, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 403 of the GNPTAB protein (p.Ile403Thr). |
Mendelics | RCV002247409 | SCV002516504 | pathogenic | Mucolipidosis type II | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000032291 | SCV000055935 | not provided | Pseudo-Hurler polydystrophy | no assertion provided | literature only |