ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.1195C>T (p.His399Tyr) (rs199476376)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672049 SCV000797108 uncertain significance Metachromatic leukodystrophy 2018-01-12 criteria provided, single submitter clinical testing
Invitae RCV000672049 SCV001225560 pathogenic Metachromatic leukodystrophy 2020-07-30 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 399 of the ARSA protein (p.His399Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs199476376, ExAC 0.002%). This variant has been observed in combination with another ARSA variant in several individuals affected with metachromatic leukodystrophy (MLD) (PMID: 9452102, 20339381, 28762252). This variant is also known as 1189C>T or H397Y in the literature. ClinVar contains an entry for this variant (Variation ID: 68117). This variant has been reported to affect ARSA enzyme activity in vitro (PMID: 9452102, 28762252). For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000058947 SCV000090468 not provided not provided no assertion provided not provided

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