ClinVar Miner

Submissions for variant NM_020166.5(MCCC1):c.1147G>A (p.Glu383Lys)

gnomAD frequency: 0.00001  dbSNP: rs1333357031
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001325461 SCV001516453 uncertain significance 3-methylcrotonyl-CoA carboxylase 1 deficiency 2021-08-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002509663 SCV002819539 uncertain significance not specified 2022-12-14 criteria provided, single submitter clinical testing Variant summary: MCCC1 c.1147G>A (p.Glu383Lys) results in a conservative amino acid change located in the biotin carboxylase, C-terminal domain (IPR005482) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251446 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1147G>A has been reported in the literature in settings of newborn screening where it has been observed in the heterozygous state (no second variant identified) in asymptomatic individuals presenting with a mild phenotype suggestive of Methylcrotonyl-CoA Carboxylase Deficiency in the first months of life, consistent with carrier status (e.g. Fonseca_2016, Navarrete_2019). However, these reports do 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. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV001325461 SCV002079104 uncertain significance 3-methylcrotonyl-CoA carboxylase 1 deficiency 2020-01-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.