Submissions for variant NM_022132.5(MCCC2):c.1208A>C (p.Asn403Thr)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002624342	SCV003515257	pathogenic	3-methylcrotonyl-CoA carboxylase 2 deficiency	2023-09-10	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asn403 amino acid residue in MCCC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MCCC2 protein function. ClinVar contains an entry for this variant (Variation ID: 2196635). This missense change has been observed in individual(s) with 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 16835865; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 403 of the MCCC2 protein (p.Asn403Thr).
Baylor Genetics	RCV002624342	SCV004194359	likely pathogenic	3-methylcrotonyl-CoA carboxylase 2 deficiency	2024-01-04	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002624342	SCV005666618	likely pathogenic	3-methylcrotonyl-CoA carboxylase 2 deficiency	2024-05-21	criteria provided, single submitter	clinical testing