ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.1114C>T (p.Arg372Trp) (rs74315476)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723522 SCV000110793 pathogenic not provided 2013-06-03 criteria provided, single submitter clinical testing
Counsyl RCV000078933 SCV000486167 likely pathogenic Metachromatic leukodystrophy 2016-04-12 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000078933 SCV000915982 pathogenic Metachromatic leukodystrophy 2017-09-01 criteria provided, single submitter clinical testing The ARSA c.1114C>T (p.Arg372Trp) missense variant has been reported in at least four studies and is found in four children with arylsulfatase A deficiency, or metachromatic leukodystrophy, including in three individuals in a homozygous state and in one individual in a compound heterozygous state (Heinisch et al. 1995; Bertelli et al. 2006; Grossi et al. 2008; Biffi et al. 2008). One of the homozygous individuals carried the variant on a complex allele with a second missense variant in cis (Grossi et al. 2008). The p.Arg372Trp variant was absent from 100 control alleles and is reported at a frequency of 0.000116 in the East Asian population of the Exome Aggregation Consortium. Expression analysis in COS-7 and BHK cells found the p.Arg372Trp variant to be associated with significantly reduced ARSA activity compared to wild type (Heinisch et al. 1995; Bertelli et al. 2006; Grossi et al. 2008; Biffi et al. 2008). In addition, expression analysis of the complex allele showed further reduction in activity in comparison to the p.Arg372Trp or the second missense variant individually (Grossi et al. 2008). Based on the collective evidence, the p.Arg372Trp variant is classified as pathogenic for arylsulfatase A deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000003227 SCV000023385 pathogenic Metachromatic leukodystrophy, severe 2018-11-07 no assertion criteria provided literature only

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