ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.449C>T (p.Pro150Leu)

dbSNP: rs199476375
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000631449 SCV000752526 pathogenic Metachromatic leukodystrophy 2023-12-25 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 150 of the ARSA protein (p.Pro150Leu). This variant is present in population databases (rs199476375, gnomAD 0.003%). This missense change has been observed in individual(s) with metachromatic leukodystrophy (PMID: 10381328, 16678723, 18786133). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as p.Pro148Leu. ClinVar contains an entry for this variant (Variation ID: 68134). 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%. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000058965 SCV001245880 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000631449 SCV001251776 likely pathogenic Metachromatic leukodystrophy 2020-05-03 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000631449 SCV001976398 pathogenic Metachromatic leukodystrophy 2021-09-20 criteria provided, single submitter clinical testing This variant was identified as compound heterozygous with NM_000487.6:c.1156C>T.
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital RCV000631449 SCV001984007 pathogenic Metachromatic leukodystrophy 2021-03-11 criteria provided, single submitter clinical testing
GeneDx RCV000058965 SCV002562680 likely pathogenic not provided 2022-02-07 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect on enzyme function (Biffi et al., 2008); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 10381328, Han_2014_thesis, 16678723, 18786133, 30828547, 31186049, 33185815)
UniProtKB/Swiss-Prot RCV000058965 SCV000090486 not provided not provided no assertion provided not provided

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