ClinVar Miner

Submissions for variant NM_052845.4(MMAB):c.394T>C (p.Cys132Arg) (rs147457956)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000443124 SCV000513638 likely benign not specified 2017-11-02 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000824472 SCV000884121 uncertain significance Vitamin B12-responsive methylmalonic acidemia type cblB 2019-02-28 criteria provided, single submitter clinical testing The MMAB c.394T>C; p.Cys132Arg variant (rs147457956) has been reported in the heterozygous state in one individual with methylmalonic aciduria out of a cohort of 181 patients (Illson 2013). This variant is listed in the genome Aggregation Database (gnomAD) with a non-Finnish European population frequency of 0.1% (identified on 145 out of 122,430 chromosomes, including one homozygote) and is classified as likely benign in ClinVar (ID: 378149). The cysteine at position 132 is weakly conserved, considering 12 species, and computational analyses of the effects of the p.Cys132Arg variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Cys132Arg variant cannot be determined with certainty.
Invitae RCV000824472 SCV000965371 uncertain significance Vitamin B12-responsive methylmalonic acidemia type cblB 2019-03-26 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 132 of the MMAB protein (p.Cys132Arg). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is present in population databases (rs147457956, ExAC 0.2%). This variant has been observed in an individual affected with methylmalonic aciduria (PMID: 23707710). ClinVar contains an entry for this variant (Variation ID: 378149). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV000824472 SCV001270284 uncertain significance Vitamin B12-responsive methylmalonic acidemia type cblB 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.