ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.449C>T (p.Pro150Leu) (rs199476375)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000631449 SCV000752526 pathogenic Metachromatic leukodystrophy 2019-12-24 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 150 of the ARSA protein (p.Pro150Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs199476375, ExAC no frequency). This variant has been reported in combination with another ARSA variant in several individuals affected with metachromatic leukodystrophy (PMID: 10381328, 18786133, 16678723, 10381328). This variant is also known as p.Pro148Leu in the literature. 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. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000058965 SCV001245880 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000631449 SCV001251776 likely pathogenic Metachromatic leukodystrophy 2020-05-03 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000058965 SCV000090486 not provided not provided no assertion provided not provided

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