Submissions for variant NM_022132.5(MCCC2):c.455A>C (p.Lys152Thr)

dbSNP: rs1554134065

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000644022	SCV000765709	uncertain significance	3-methylcrotonyl-CoA carboxylase 2 deficiency	2021-08-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003230563	SCV003928558	uncertain significance	not specified	2023-04-25	criteria provided, single submitter	clinical testing	Variant summary: MCCC2 c.455A>C (p.Lys152Thr) results in a non-conservative amino acid change located in the Acetyl-coenzyme A carboxyltransferase, N-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251482 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.455A>C has been reported in the literature in at least one asymptomatic individual with Methylcrotonyl-CoA Carboxylase Deficiency (Grunert_2012). This report does not provide unequivocal conclusions about association of the variant with Methylcrotonyl-CoA Carboxylase Deficiency. 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: 27601257, 22642865). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.