ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.1136C>T (p.Pro379Leu)

dbSNP: rs74315478
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV002512051 SCV002821142 pathogenic not provided 2024-01-01 criteria provided, single submitter clinical testing ARSA: PM3:Very Strong, PM2, PS3:Supporting
Invitae RCV003500499 SCV004300062 pathogenic Metachromatic leukodystrophy 2023-12-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 379 of the ARSA protein (p.Pro379Leu). This variant is present in population databases (rs74315478, gnomAD 0.0009%). This missense change has been observed in individual(s) with late infantile metachromatic leukodystrophy, and is commonly reported in individuals of Habbanite Jewish ancestry (PMID: 7749412). It is commonly reported in individuals of Jewish ancestry (PMID: 7749412). This variant is also known as P377L. ClinVar contains an entry for this variant (Variation ID: 3083). 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: 7749412). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000003229 SCV000023387 pathogenic Arylsulfatase a pseudodeficiency, severe 1994-01-01 no assertion criteria provided literature only

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