ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.884G>A (p.Gly295Asp)

dbSNP: rs199476387
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001150625 SCV001311708 uncertain significance Metachromatic leukodystrophy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV001150625 SCV004300067 pathogenic Metachromatic leukodystrophy 2023-04-20 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 68155). This variant is also known as G293D. This missense change has been observed in individual(s) with metachromatic leukodystrophy (PMID: 15026521). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 295 of the ARSA protein (p.Gly295Asp). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly295 amino acid residue in ARSA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15326627, 18786133). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ARSA protein function.
UniProtKB/Swiss-Prot RCV000058986 SCV000090507 not provided not provided no assertion provided not provided

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