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

dbSNP: rs765905826

Total submissions: 6

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	2024-01-11	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. This variant is present in population databases (rs765905826, gnomAD 0.003%). This variant has been observed in individual(s) 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. 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.
CeGaT Center for Human Genetics Tuebingen	RCV001726017	SCV001962457	pathogenic	not provided	2021-11-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000169598	SCV002807769	pathogenic	Metachromatic leukodystrophy	2021-12-07	criteria provided, single submitter	clinical testing
Gelb Laboratory, University of Washington	RCV000169598	SCV005046700	not provided	Metachromatic leukodystrophy		no assertion provided	in vitro