Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169048 | SCV000220207 | likely pathogenic | Metachromatic leukodystrophy | 2014-03-30 | criteria provided, single submitter | literature only | |
Gene |
RCV000364541 | SCV000329854 | pathogenic | not provided | 2022-11-18 | criteria provided, single submitter | clinical testing | Published functional demonstrate residual enzyme activity of 6.7% compared to controls, supporting a damaging effect (Regis et al., 2002); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 18786133, 23559313, 26462614, 31589614, 18693274, 11941485) |
Centre for Mendelian Genomics, |
RCV000169048 | SCV001367112 | pathogenic | Metachromatic leukodystrophy | 2019-09-08 | criteria provided, single submitter | clinical testing | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PS3_M,PM3,PP3,PP4. |
Laboratory for Molecular Genetic Diagnostic of Neurological Diseases, |
RCV000169048 | SCV001832551 | pathogenic | Metachromatic leukodystrophy | 2021-07-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000169048 | SCV002185606 | pathogenic | Metachromatic leukodystrophy | 2023-05-27 | 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 ARSA function (PMID: 11941485). 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 ARSA protein function. ClinVar contains an entry for this variant (Variation ID: 3091). This variant is also known as E253K. This missense change has been observed in individual(s) with late infantile metachromatic leukodystrophy (PMID: 11941485, 18786133). 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 (rs74315483, gnomAD 0.0009%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 255 of the ARSA protein (p.Glu255Lys). |
OMIM | RCV000003237 | SCV000023395 | pathogenic | Metachromatic leukodystrophy, late infantile form | 2002-04-01 | no assertion criteria provided | literature only | |
Natera, |
RCV000169048 | SCV002081660 | pathogenic | Metachromatic leukodystrophy | 2021-02-21 | no assertion criteria provided | clinical testing |