Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002039088 | SCV002311824 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2021-10-06 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Glu134 amino acid residue in MCCC1. Other variant(s) that disrupt this residue have been observed in individuals with MCCC1-related conditions (PMID: 16010683), which suggests that this may be a clinically significant amino acid residue. 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 disruptive. This missense change has been observed in individual(s) with 3-methylcrotonyl-CoA carboxylase deficiency (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glycine at codon 134 of the MCCC1 protein (p.Glu134Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. |