Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000631449 | SCV000752526 | pathogenic | Metachromatic leukodystrophy | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 150 of the ARSA protein (p.Pro150Leu). This variant is present in population databases (rs199476375, gnomAD 0.003%). This missense change has been observed in individual(s) with metachromatic leukodystrophy (PMID: 10381328, 16678723, 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 also known as p.Pro148Leu. ClinVar contains an entry for this variant (Variation ID: 68134). 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. |
Ce |
RCV000058965 | SCV001245880 | pathogenic | not provided | 2017-11-01 | criteria provided, single submitter | clinical testing | |
Genomic Research Center, |
RCV000631449 | SCV001251776 | likely pathogenic | Metachromatic leukodystrophy | 2020-05-03 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000631449 | SCV001976398 | pathogenic | Metachromatic leukodystrophy | 2021-09-20 | criteria provided, single submitter | clinical testing | This variant was identified as compound heterozygous with NM_000487.6:c.1156C>T. |
Al Jalila Children's Genomics Center, |
RCV000631449 | SCV001984007 | pathogenic | Metachromatic leukodystrophy | 2021-03-11 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000058965 | SCV002562680 | likely pathogenic | not provided | 2022-02-07 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect on enzyme function (Biffi et al., 2008); 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: 10381328, Han_2014_thesis, 16678723, 18786133, 30828547, 31186049, 33185815) |
Uni |
RCV000058965 | SCV000090486 | not provided | not provided | no assertion provided | not provided |