ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.862A>C (p.Thr288Pro)

dbSNP: rs28940894
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000795605 SCV000935073 pathogenic Metachromatic leukodystrophy 2024-07-24 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 288 of the ARSA protein (p.Thr288Pro). This variant is present in population databases (rs28940894, gnomAD 0.06%). This missense change has been observed in individual(s) with metachromatic leukodystrophy (PMID: 11061266, 12035837). This variant is also known as Thr286Pro. ClinVar contains an entry for this variant (Variation ID: 3090). 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%. Experimental studies have shown that this missense change affects ARSA function (PMID: 12035837). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000795605 SCV005656808 likely pathogenic Metachromatic leukodystrophy 2024-05-24 criteria provided, single submitter clinical testing
OMIM RCV000003236 SCV000023394 pathogenic Metachromatic leukodystrophy, adult type 2000-10-10 no assertion criteria provided literature only
Natera, Inc. RCV000795605 SCV002081655 pathogenic Metachromatic leukodystrophy 2020-09-23 no assertion criteria provided clinical testing
Gelb Laboratory, University of Washington RCV000795605 SCV005046530 not provided Metachromatic leukodystrophy no assertion provided in vitro
PreventionGenetics, part of Exact Sciences RCV004755703 SCV005363347 likely pathogenic ARSA-related disorder 2024-05-02 no assertion criteria provided clinical testing The ARSA c.862A>C variant is predicted to result in the amino acid substitution p.Thr288Pro. This variant was reported in the homozygous state in two individuals with acute left hand weakness, demyelinating polyneuropathy and arylsulfatase deficiency (described as p.Thr286Pro, Felice et al. 2000. PubMed ID: 11061266, Coulter-Mackie et al. 2002. PubMed ID: 12035837). This variant is reported in 0.066% of alleles in individuals of South Asian descent in gnomAD. This variant is interpreted as likely pathogenic.

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