ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.1289T>C (p.Leu430Pro)

dbSNP: rs199476392
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000058949 SCV002758952 likely pathogenic not provided 2022-12-01 criteria provided, single submitter clinical testing Reported previously in a patient with juvenile metachromatic leukodystrophy who harbored a second variant in the ARSA gene; phase unknown (Cesani et al., 2015); Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as p.L428P; This variant is associated with the following publications: (PMID: 26462614, 18693274, 26659599, 27915290, 9272717)
Labcorp Genetics (formerly Invitae), Labcorp RCV002514296 SCV003513262 pathogenic Metachromatic leukodystrophy 2023-08-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 430 of the ARSA protein (p.Leu430Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of metachromatic leukodystrophy (PMID: 9272717, 26462614; Invitae). 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.L428P. ClinVar contains an entry for this variant (Variation ID: 68119). 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.
Revvity Omics, Revvity RCV002514296 SCV003825024 uncertain significance Metachromatic leukodystrophy 2021-08-11 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000058949 SCV000090470 not provided not provided no assertion provided not provided
Gelb Laboratory, University of Washington RCV002514296 SCV005046743 not provided Metachromatic leukodystrophy no assertion provided in vitro

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