Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV000584948 | SCV000693175 | pathogenic | not provided | 2021-03-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000002001 | SCV004293740 | pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2023-02-11 | criteria provided, single submitter | clinical testing | Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change results in activation of a cryptic splice site, deletes the last 19bp of exon 8 and introduces a premature termination codon (PMID: 16010683). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 268 of the MCCC2 protein (p.Arg268Thr). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with 3 methylcrotonyl-CoA carboxylase deficiency (PMID: 11406611, 16835865). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1924). |
| OMIM | RCV000002001 | SCV000022159 | pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2001-06-01 | no assertion criteria provided | literature only |