Submissions for variant NM_022132.5(MCCC2):c.1375C>T (p.Pro459Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV003470072	SCV004194332	likely pathogenic	3-methylcrotonyl-CoA carboxylase 2 deficiency	2023-10-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004783065	SCV005394446	uncertain significance	not specified	2024-09-13	criteria provided, single submitter	clinical testing	Variant summary: MCCC2 c.1375C>T (p.Pro459Ser) results in a non-conservative amino acid change located in the Acetyl-coenzyme A carboxyltransferase, C-terminal domain (IPR011763) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 251342 control chromosomes. c.1375C>T has been reported in the literature in compound heterozygous individuals affected with Methylcrotonyl-CoA Carboxylase Deficiency (Jung_2012, Cho_2012). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 22150417, 22030835). ClinVar contains an entry for this variant (Variation ID: 2676476). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.