Submissions for variant NM_000487.6(ARSA):c.257G>T (p.Arg86Leu)

dbSNP: rs74315458

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000672928	SCV000798084	uncertain significance	Metachromatic leukodystrophy	2018-02-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000672928	SCV005394752	likely pathogenic	Metachromatic leukodystrophy	2024-09-24	criteria provided, single submitter	clinical testing	Variant summary: ARSA c.257G>T (p.Arg86Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 225598 control chromosomes (gnomAD). c.257G>T has been reported in the literature in an individual affected with Metachromatic Leukodystrophy (Luzi_2013). Other variants affecting the same codon have been classified as pathogenic by our lab (c.256C>T/p.Arg86Trp, c.257G>A/p.Arg86Gln), supporting the critical relevance of codon 86 to ARSA protein function. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 24001781). ClinVar contains an entry for this variant (Variation ID: 556866). Based on the evidence outlined above, the variant was classified as likely pathogenic.