ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.1663A>G (p.Lys555Glu)

gnomAD frequency: 0.00004  dbSNP: rs1257849672
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001309509 SCV001499010 uncertain significance 3-methylcrotonyl-CoA carboxylase 2 deficiency 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 555 of the MCCC2 protein (p.Lys555Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individuals with clinical features of 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 16835865; Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844282 SCV002103967 uncertain significance not specified 2022-02-10 criteria provided, single submitter clinical testing Variant summary: MCCC2 c.1663A>G (p.Lys555Glu) results in a conservative amino acid change located in the Acetyl-coenzyme A carboxyltransferase, C-terminal domain (IPR011763) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251430 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1663A>G has been reported in a mother with moderately elevated biochemical markers in the screening for MCCD, identified through her infant's newborn screening. The mother was compound heterozygous with a pathogenic variant but remained clinically asymptomatic (Stadler_2006). This report does not provide unequivocal conclusions about association of the variant with Methylcrotonyl-CoA Carboxylase Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV001309509 SCV002084927 uncertain significance 3-methylcrotonyl-CoA carboxylase 2 deficiency 2021-02-02 no assertion criteria provided clinical testing

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.