Submissions for variant NM_022132.5(MCCC2):c.632T>G (p.Val211Gly)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003059951	SCV003195197	likely pathogenic	not provided	2022-07-18	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported previously in a data set of newborns undergoing exome sequencing for inborn errors of metabolism; clinical information not provided (Adhikari et al., 2020); This variant is associated with the following publications: (PMID: 32778825)
Labcorp Genetics (formerly Invitae), Labcorp	RCV003059950	SCV003519274	uncertain significance	3-methylcrotonyl-CoA carboxylase 2 deficiency	2022-07-25	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 211 of the MCCC2 protein (p.Val211Gly). 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 (Invitae). 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. 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, Revvity	RCV003059950	SCV004236320	uncertain significance	3-methylcrotonyl-CoA carboxylase 2 deficiency	2023-03-13	criteria provided, single submitter	clinical testing