ClinVar Miner

Submissions for variant NM_052845.4(MMAB):c.568C>T (p.Arg190Cys)

gnomAD frequency: 0.00002  dbSNP: rs398124434
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000790778 SCV000700308 pathogenic not provided 2017-05-02 criteria provided, single submitter clinical testing
Invitae RCV000203347 SCV002154498 pathogenic Methylmalonic aciduria, cblB type 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 190 of the MMAB protein (p.Arg190Cys). This variant is present in population databases (rs398124434, gnomAD 0.003%). This missense change has been observed in individuals with clinical features of methylmalonic aciduria cobalamin B type (PMID: 16410054, 24059531, 29039164). ClinVar contains an entry for this variant (Variation ID: 96244). 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 MMAB protein function. Experimental studies have shown that this missense change affects MMAB function (PMID: 19625202, 29197662). This variant disrupts the p.Arg190 amino acid residue in MMAB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16410054, 16439175, 19625202; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000203347 SCV002812317 likely pathogenic Methylmalonic aciduria, cblB type 2022-02-17 criteria provided, single submitter clinical testing
Baylor Genetics RCV000203347 SCV004193156 pathogenic Methylmalonic aciduria, cblB type 2021-11-20 criteria provided, single submitter clinical testing
GeneReviews RCV000203347 SCV000258527 not provided Methylmalonic aciduria, cblB type no assertion provided literature only
Counsyl RCV000203347 SCV001132248 likely pathogenic Methylmalonic aciduria, cblB type 2019-01-09 no assertion criteria provided clinical testing
Baumgartner lab, University Children's Hospital Zurich RCV000203347 SCV001738799 pathogenic Methylmalonic aciduria, cblB type 2021-06-01 no assertion criteria provided clinical testing

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