Submissions for variant NM_000487.6(ARSA):c.1227_1228del (p.Thr410fs)

dbSNP: rs2082647866

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001280565	SCV001467767	likely pathogenic	Metachromatic leukodystrophy	2020-12-07	criteria provided, single submitter	clinical testing	Variant summary: ARSA c.1227_1228delTA (p.Thr410HisfsX16) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 238760 control chromosomes. c.1227_1228delTA has been reported in the literature as 2324delAT in at-least one homozygous individual affected with the late infantile form of Metachromatic Leukodystrophy (Regis_1995). At least one publication reports experimental evidence evaluating enzyme activity in cultured fibroblasts. However, this report does not allow convincing conclusions about the variant effect due to no information on a reference range for control activity levels (Regis_1995). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.