ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.1195C>T (p.His399Tyr)

gnomAD frequency: 0.00001  dbSNP: rs199476376
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672049 SCV000797108 uncertain significance Metachromatic leukodystrophy 2018-01-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000672049 SCV001225560 pathogenic Metachromatic leukodystrophy 2023-09-29 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 399 of the ARSA protein (p.His399Tyr). This variant is present in population databases (rs199476376, gnomAD 0.0009%). This missense change has been observed in individual(s) with metachromatic leukodystrophy (MLD) (PMID: 9452102, 20339381, 28762252). This variant is also known as 1189C>T or H397Y. ClinVar contains an entry for this variant (Variation ID: 68117). 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: 9452102, 28762252). For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000058947 SCV000090468 not provided not provided no assertion provided not provided
Gelb Laboratory, University of Washington RCV000672049 SCV005046769 not provided Metachromatic leukodystrophy no assertion provided in vitro

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