Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001237411 | SCV001410170 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 109 of the MCCC2 protein (p.Tyr109Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MCCC2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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, |
RCV004782679 | SCV005395422 | uncertain significance | not specified | 2024-09-18 | criteria provided, single submitter | clinical testing | Variant summary: MCCC2 c.326A>G (p.Tyr109Cys) results in a non-conservative amino acid change located in the acetyl-coenzyme A carboxyltransferase, N-terminal domain (IPR011762) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251476 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.326A>G has been reported in the literature in at least an individual affected with Methylcrotonyl-CoA Carboxylase Deficiency (example: Cheng_2023). These report(s) do 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. The following publication has been ascertained in the context of this evaluation (PMID: 36822454). ClinVar contains an entry for this variant (Variation ID: 963392). Based on the evidence outlined above, the variant was classified as uncertain significance. |