NM_022132.5(MCCC2):c.1690T>C (p.Ter564Gln) AND Methylcrotonyl-CoA carboxylase deficiency

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Apr 27, 2026
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001271415.6

Allele description [Variation Report for NM_022132.5(MCCC2):c.1690T>C (p.Ter564Gln)]

NM_022132.5(MCCC2):c.1690T>C (p.Ter564Gln)

Gene:

MCCC2:methylcrotonyl-CoA carboxylase subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q13.2

Genomic location:

Preferred name:

NM_022132.5(MCCC2):c.1690T>C (p.Ter564Gln)

Other names:

*564Q; *526Q

HGVS:

NC_000005.10:g.71656858T>C
NG_008882.1:g.74571T>C
NM_001363147.1:c.1576T>C
NM_022132.5:c.1690T>CMANE SELECT
NP_001350076.1:p.Ter526Gln
NP_071415.1:p.Ter564Gln
NC_000005.9:g.70952685T>C
NM_022132.4:c.1690T>C

Links:

dbSNP: rs751970792

Molecular consequence:

NM_001363147.1:c.1576T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_022132.5:c.1690T>C - stop lost - [Sequence Ontology: SO:0001578]

Condition(s)

Name:: Methylcrotonyl-CoA carboxylase deficiency
Synonyms:: Deficiency of methylcrotonoyl-CoA carboxylase; 3 Methylcrotonylglycinuria; 3-MCC Deficiency
Identifiers:: MONDO: MONDO:0018950; MedGen: C4551505; OMIM: PS210200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001452541	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 16, 2020)	germline	clinical testing
SCV004029650	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Apr 27, 2026)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001452541

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Sep 16, 2020)

germline

clinical testing

SCV004029650

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Apr 27, 2026)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

3-Methylcrotonyl-CoA carboxylase deficiency: mutation analysis in 28 probands, 9 symptomatic and 19 detected by newborn screening.

Dantas MF, Suormala T, Randolph A, Coelho D, Fowler B, Valle D, Baumgartner MR.

Hum Mutat. 2005 Aug;26(2):164.

PubMed [citation]

PMID:: 16010683

Details of each submission

From Natera, Inc., SCV001452541.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004029650.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: MCCC2 c.1690T>C (p.X564GlnextX3) changes the termination codon and is predicted to lead to an extended protein with additional amino acids added to the normal C-terminus. The variant allele was found at a frequency of 2.8e-05 in 251414 control chromosomes (gnomAD). c.1690T>C has been observed in individual(s) affected with pathognomic clinical and metabolic features of Methylcrotonyl-CoA Carboxylase Deficiency (example: Dantas_2005 overlapping with Grunert_2012 and internal data). These data indicate that the variant is likely to 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: 16010683, 22642865). ClinVar contains an entry for this variant (Variation ID: 570791). Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 9, 2026

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