Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000699138 | SCV000827835 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2021-12-25 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 576604). This missense change has been observed in individual(s) with clinical features of MCCC2-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 333 of the MCCC2 protein (p.Glu333Asp). This variant also falls at the last nucleotide of exon 10, which is part of the consensus splice site for this exon. 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: "Benign"; Align-GVGD: "Class C35"). 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. |