ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.970G>A (p.Ala324Thr)

dbSNP: rs780387525
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665776 SCV000789948 likely pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2017-03-01 criteria provided, single submitter clinical testing
Invitae RCV001376589 SCV001234141 pathogenic not provided 2023-09-01 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: 550893). This missense change has been observed in individual(s) with methylmalonic aciduria (PMID: 15781192, 16281286, 17957493; Invitae). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 324 of the MUT protein (p.Ala324Thr).
Fulgent Genetics, Fulgent Genetics RCV000665776 SCV002799616 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2022-05-12 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003411570 SCV004113040 pathogenic MMUT-related condition 2023-02-15 criteria provided, single submitter clinical testing The MMUT c.970G>A variant is predicted to result in the amino acid substitution p.Ala324Thr. This variant has been reported along with a second MMUT variant in individuals with MMUT-associated methylmalonic acidemia (MMA) (Martinez et al. 2005. PubMed ID: 15781192; Worgan et al. 2006. PubMed ID: 16281286; Merinero et al. 2008. PubMed ID: 17957493; Chu et al. 2016. PubMed ID: 27233228; Han et al. 2019. PubMed ID: 31466887). This variant is reported in 0.014% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-49421411-C-T). Based on the available evidence, this variant is interpreted as pathogenic.
Natera, Inc. RCV001835905 SCV002077387 pathogenic Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency 2021-06-30 no assertion criteria provided clinical testing

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