Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
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, |
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, |
RCV001309509 | SCV002084927 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2021-02-02 | no assertion criteria provided | clinical testing |