ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.677C>T (p.Ala226Val)

gnomAD frequency: 0.00003  dbSNP: rs74315468
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000343115 SCV000338915 uncertain significance not provided 2016-10-27 criteria provided, single submitter clinical testing
Invitae RCV000003217 SCV000752524 pathogenic Metachromatic leukodystrophy 2023-06-06 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 226 of the ARSA protein (p.Ala226Val). For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 3071). This variant is also known as A224V. This missense change has been observed in individual(s) with metachromatic leukodystrophy (PMID: 7906588; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs74315468, gnomAD 0.01%).
GeneDx RCV000343115 SCV002588114 likely pathogenic not provided 2022-10-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as p.A224V; This variant is associated with the following publications: (PMID: 7967499, 7906588, 16546179, 27535533)
OMIM RCV000003217 SCV000023375 pathogenic Metachromatic leukodystrophy 1993-12-01 no assertion criteria provided literature only

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