Submissions for variant NM_020166.5(MCCC1):c.2088dup (p.Val697fs)

dbSNP: rs746267545

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000817601	SCV000958170	likely pathogenic	3-methylcrotonyl-CoA carboxylase 1 deficiency	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val697Serfs*19) in the MCCC1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 29 amino acid(s) of the MCCC1 protein. This variant is present in population databases (rs746267545, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with methylcrotonyl-CoA carboxylase deficiency (PMID: 22642865; Invitae). ClinVar contains an entry for this variant (Variation ID: 660413). This variant disrupts the C-terminus of the MCCC1 protein. Other variant(s) that disrupt this region (p.His708Glnfs*8) have been observed in individuals with MCCC1-related conditions (PMID: 22642865). This suggests that this may be a clinically significant region of the protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Revvity Omics, Revvity	RCV000817601	SCV003833899	likely pathogenic	3-methylcrotonyl-CoA carboxylase 1 deficiency	2022-10-10	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000817601	SCV004194275	pathogenic	3-methylcrotonyl-CoA carboxylase 1 deficiency	2023-07-23	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528975	SCV001741647	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528975	SCV001965025	likely pathogenic	not provided		no assertion criteria provided	clinical testing