ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.256C>T (p.Arg86Trp) (rs199476352)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409776 SCV000487120 pathogenic Metachromatic leukodystrophy 2016-10-10 criteria provided, single submitter clinical testing
Invitae RCV000409776 SCV001229305 pathogenic Metachromatic leukodystrophy 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 86 of the ARSA protein (p.Arg86Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with another ARSA variant in individuals affected with metachromatic leukodystrophy (PMID: 10477432, 18786133). This variant is also known as c.399C>T, p.R84W in the literature. ClinVar contains an entry for this variant (Variation ID: 68126). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg86 amino acid residue in ARSA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12809637, 1353340, 26462614, 18693274). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV001090098 SCV001245562 uncertain significance Frontotemporal dementia 2019-10-28 criteria provided, single submitter research
UniProtKB/Swiss-Prot RCV000058956 SCV000090477 not provided not provided no assertion provided not provided

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