ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.1223_1231del (p.Ser408_Thr410del) (rs765905826)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169598 SCV000221110 likely pathogenic Metachromatic leukodystrophy 2015-02-02 criteria provided, single submitter literature only
Invitae RCV000169598 SCV001406500 pathogenic Metachromatic leukodystrophy 2020-08-17 criteria provided, single submitter clinical testing This variant, c.1223_1231del, results in the deletion of 3 amino acid(s) of the ARSA protein (p.Ser408_Thr410del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in combination with another ARSA variant in individuals affected with metachromatic leukodystrophy (PMID: 9490297, 12809637, 18786133, 22993277, 23559313). This variant is also known as c.1215_1223del, c.1216-24del9, c.1216del9, c.1217_1225del, and 2320del9 in the literature. ClinVar contains an entry for this variant (Variation ID: 189170). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169598 SCV001467946 pathogenic Metachromatic leukodystrophy 2020-12-11 criteria provided, single submitter clinical testing Variant summary: ARSA c.1223_1231delGTGATACCA (p.Ser408_Thr410del) results in an in-frame deletion that is predicted to remove three amino acids from the encoded protein. The variant allele was found at a frequency of 8.4e-06 in 238866 control chromosomes. c.1223_1231delGTGATACCA has been reported in the literature in multiple individuals affected with Metachromatic Leukodystrophy (Regis_1998, Biffi_2008, Cesani_2015, Rafi_2003, Galla_2013). These data indicate that the variant is very likely to be associated with disease. The variant results in significantly reduced enzyme activity (Regis_1998). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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