ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.1115G>A (p.Arg372Gln) (rs74315477)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000544790 SCV000627135 uncertain significance Metachromatic leukodystrophy 2017-04-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 372 of the ARSA protein (p.Arg372Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs74315477, ExAC 0.002%). This variant has been reported in the literature in a mildly affected individual (PMID: 7866401). ClinVar contains an entry for this variant (Variation ID: 3082). This variant is also known as p.Arg370Gln or p.R370Q in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Arg370Trp) has been shown to cause diminished enzyme activity in vitro (PMID: 7825603). This suggests that the arginine residue is critical for ARSA protein function and that other missense substitutions at this position may also impact protein function. In summary, this variant is a rare missense change that has been observed in affected individual but has uncertain impact on protein function.  Additional genetic or functional data are needed to assess the clinical relevance of this variant. For these reasons, this change has been classified as a Variant of Uncertain Significance.
Counsyl RCV000544790 SCV000800496 uncertain significance Metachromatic leukodystrophy 2017-02-09 criteria provided, single submitter clinical testing
OMIM RCV000003228 SCV000023386 pathogenic Metachromatic leukodystrophy, mild 2018-11-07 no assertion criteria provided literature only

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