ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.592G>A (p.Gly198Arg)

gnomAD frequency: 0.00002  dbSNP: rs144393886
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001059607 SCV001224234 uncertain significance Metachromatic leukodystrophy 2022-07-05 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 198 of the ARSA protein (p.Gly198Arg). This variant is present in population databases (rs144393886, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ARSA-related conditions. ClinVar contains an entry for this variant (Variation ID: 854531). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002553864 SCV003608265 likely benign Inborn genetic diseases 2022-10-13 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity RCV001059607 SCV003825027 uncertain significance Metachromatic leukodystrophy 2020-11-13 criteria provided, single submitter clinical testing
Natera, Inc. RCV001059607 SCV001456235 uncertain significance Metachromatic leukodystrophy 2020-02-13 no assertion criteria provided clinical testing
Gelb Laboratory, University of Washington RCV001059607 SCV005046599 not provided Metachromatic leukodystrophy no assertion provided in vitro

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