ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.640G>C (p.Ala214Pro)

dbSNP: rs199476341
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001380269 SCV001578269 pathogenic Metachromatic leukodystrophy 2022-06-14 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 214 of the ARSA protein (p.Ala214Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with metachromatic leukodystrophy (PMID: 18786133). This variant is also known as p.Ala212Pro. ClinVar contains an entry for this variant (Variation ID: 68145). 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. Experimental studies have shown that this missense change affects ARSA function (PMID: 18693274, 19606494). This variant disrupts the p.Ala214 amino acid residue in ARSA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7906588, 9090526, 9192271, 14517960, 26462614). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000058976 SCV000090497 not provided not provided no assertion provided not provided
Natera, Inc. RCV001380269 SCV002081666 pathogenic Metachromatic leukodystrophy 2021-07-27 no assertion criteria provided clinical testing
Gelb Laboratory, University of Washington RCV001380269 SCV005046582 not provided Metachromatic leukodystrophy no assertion provided in vitro

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