Submissions for variant NM_000487.6(ARSA):c.697C>A (p.Pro233Thr)

dbSNP: rs74315469

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003387714	SCV004099984	uncertain significance	not specified	2023-09-01	criteria provided, single submitter	clinical testing	Variant summary: ARSA c.697C>A (p.Pro233Thr) 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 250716 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.697C>A has been reported in the literature in individual(s) affected with Metachromatic Leukodystrophy (example, Gieselmann_1994). These report(s) do not provide unequivocal conclusions about association of the variant with Metachromatic Leukodystrophy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 7866401). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic, which is not based on a clinical testing but literature reviewing. Based on the evidence outlined above, the variant was classified as uncertain significance.
OMIM	RCV000003218	SCV000023376	pathogenic	Metachromatic leukodystrophy	2016-10-11	no assertion criteria provided	literature only