ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.413C>T (p.Pro138Leu) (rs74315462)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000675081 SCV000800583 uncertain significance Metachromatic leukodystrophy 2017-08-30 criteria provided, single submitter clinical testing
Invitae RCV000675081 SCV001592679 pathogenic Metachromatic leukodystrophy 2020-08-20 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 138 of the ARSA protein (p.Pro138Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs74315462, ExAC 0.01%). This variant has been observed to be homozygous in an individual affected with metachromatic leukodystrophy (PMID: 7860068). This variant is also known as P136L. ClinVar contains an entry for this variant (Variation ID: 3064). This variant has been reported to affect ARSA protein function (PMID: 7860068). This variant disrupts the p.Pro138 amino acid residue in ARSA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22854541). 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.
OMIM RCV000003210 SCV000023368 pathogenic Metachromatic leukodystrophy, severe 2018-11-07 no assertion criteria provided literature only

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