ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.566A>T (p.Asn189Ile)

dbSNP: rs200908035
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
University Children's Hospital, University of Zurich RCV000236505 SCV000262787 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000236505 SCV002060053 likely pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2021-11-16 criteria provided, single submitter clinical testing NM_000255.3(MMUT):c.566A>T(N189I) is a missense variant classified as likely pathogenic in the context of methylmalonic acidemia, MMUT-related. N189I has been observed in cases with relevant disease (PMID: 27167370, 27233228). Functional assessments of this variant are available in the literature (PMID: 27167370). Internal structural analysis of the variant is supportive of pathogenicity. N189I has been observed in population frequency databases (gnomAD: NFE <0.001%). In summary, NM_000255.3(MMUT):c.566A>T(N189I) is a missense variant that has both functional and internal structural support for pathogenicity and has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Labcorp Genetics (formerly Invitae), Labcorp RCV001853320 SCV002309697 pathogenic not provided 2023-03-08 criteria provided, single submitter clinical testing 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 MUT protein function. ClinVar contains an entry for this variant (Variation ID: 222915). This missense change has been observed in individual(s) with methylmalonic aciduria (PMID: 27167370, 27233228). This variant is present in population databases (rs200908035, gnomAD 0.0009%). This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 189 of the MUT protein (p.Asn189Ile).
Fulgent Genetics, Fulgent Genetics RCV000236505 SCV002806762 likely pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2022-05-14 criteria provided, single submitter clinical testing

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