ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.257G>A (p.Arg86Gln) (rs74315458)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000723563 SCV000227131 pathogenic not provided 2014-06-13 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000020316 SCV000893601 pathogenic Metachromatic leukodystrophy 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000020316 SCV000947631 pathogenic Metachromatic leukodystrophy 2020-10-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 86 of the ARSA protein (p.Arg86Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs74315458, ExAC 0.04%). This variant has been observed in combination with another ARSA variant in individuals affected with metachromatic leukodystrophy (PMID: 12809637, 1353340, 26462614, 18693274). This variant is also known as c.251G>A, p.Arg84Gln in the literature. ClinVar contains an entry for this variant (Variation ID: 21186). Experimental studies have shown that this missense change results in an ARSA protein with null enzymatic activity (PMID: 1353340). Variants that disrupt the p.86 amino acid residue in ARSA have been observed in affected individuals (PMID: 18786133, 10477432, 26462614, 24001781). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000020316 SCV001163458 pathogenic Metachromatic leukodystrophy criteria provided, single submitter clinical testing
OMIM RCV000003205 SCV000023363 pathogenic Metachromatic leukodystrophy, late-onset 1992-03-01 no assertion criteria provided literature only
GeneReviews RCV000020316 SCV000040691 pathologic Metachromatic leukodystrophy 2011-08-25 no assertion criteria provided curation Converted during submission to Pathogenic.
Natera, Inc. RCV000020316 SCV001452358 pathogenic Metachromatic leukodystrophy 2020-09-16 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000723563 SCV001743512 pathogenic not provided no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000723563 SCV001798473 pathogenic not provided no assertion criteria provided clinical testing

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