Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000689580 | SCV000817237 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2022-06-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 209 of the MCCC1 protein (p.Gly209Asp). This variant is present in population databases (rs186209189, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MCCC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 569048). 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. 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. |
Revvity Omics, |
RCV000689580 | SCV003810807 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2022-10-10 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003411603 | SCV004113357 | uncertain significance | MCCC1-related disorder | 2023-08-07 | criteria provided, single submitter | clinical testing | The MCCC1 c.626G>A variant is predicted to result in the amino acid substitution p.Gly209Asp. To our knowledge, this variant has not been reported in the literature. A different substitution affecting the same amino acid (p.Gly209Ala) was reported along with a loss-of-function variant in a patient with 3-MCC deficiency (Yang et al. 2015. PubMed ID: 25382614). Of note, the p.Gly209 amino acid is located in the enzyme ATP binding pocket (Yang et al. 2015. PubMed ID: 25382614). This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-182789011-C-T). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |