Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000803574 | SCV000943452 | pathogenic | Metachromatic leukodystrophy | 2023-11-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 101 of the ARSA protein (p.Gly101Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with metachromatic leukodystrophy (PMID: 10477432, 26553228, 27374302, 27779215, 30057904). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as Gly99Val (445G>T) or Gly15Val. ClinVar contains an entry for this variant (Variation ID: 68129). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Uni |
RCV000058960 | SCV000090481 | not provided | not provided | no assertion provided | not provided | ||
Natera, |
RCV000803574 | SCV002083902 | pathogenic | Metachromatic leukodystrophy | 2020-08-04 | no assertion criteria provided | clinical testing |