Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000807706 | SCV000947774 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with arginine at codon 577 of the MCCC1 protein (p.Gln577Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs749473644, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with MCCC1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Prevention |
RCV003975327 | SCV004794304 | uncertain significance | MCCC1-related disorder | 2024-01-30 | no assertion criteria provided | clinical testing | The MCCC1 c.1730A>G variant is predicted to result in the amino acid substitution p.Gln577Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0018% of alleles in individuals of European (non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |