ClinVar Miner

Submissions for variant NM_052845.4(MMAB):c.403G>A (p.Ala135Thr) (rs35648932)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482151 SCV000568147 uncertain significance not provided 2018-08-01 criteria provided, single submitter clinical testing The A135T variant in the MMAB gene has previously been reported in individuals with methylmalonic acidemia (MMA) cblB type who also harbored the R191W pathogenic variant and two of these patients were also reported to be heterozygous for a Y219C variant in MMAB; the phase of these variants was not determined (Dobson et al., 2002; Lerner-Ellis et al., 2006). The A135T variant is observed in 83/6162 (1.4%) alleles from individuals of African background, including 2 homozygous individuals in the ExAC dataset (Lek et al., 2016). The A135T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000203394 SCV000763804 benign Vitamin B12-responsive methylmalonic acidemia type cblB 2020-12-04 criteria provided, single submitter clinical testing
GeneReviews RCV000203394 SCV000258525 pathogenic Vitamin B12-responsive methylmalonic acidemia type cblB 2016-01-07 no assertion criteria provided literature only
Natera, Inc. RCV000203394 SCV001455425 benign Vitamin B12-responsive methylmalonic acidemia type cblB 2020-01-12 no assertion criteria provided clinical testing

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