NM_022132.5(MCCC2):c.1690T>C (p.Ter564Gln) AND 3-methylcrotonyl-CoA carboxylase 2 deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 23, 2025
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:: RCV000691743.21

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:: 3-methylcrotonyl-CoA carboxylase 2 deficiency
Synonyms:: METHYLCROTONYLGLYCINURIA, TYPE II; 3 alpha methylcrotonyl-CoA carboxylase 2 deficiency; 3 alpha methylcrotonylglycinuria 2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008862; MedGen: C1859499; Orphanet: 6; OMIM: 210210

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000819533	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 23, 2025)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16010683, 22642865, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000819533

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 23, 2025)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

3-methylcrotonyl-CoA carboxylase deficiency: clinical, biochemical, enzymatic and molecular studies in 88 individuals.

Grünert SC, Stucki M, Morscher RJ, Suormala T, Bürer C, Burda P, Christensen E, Ficicioglu C, Herwig J, Kölker S, Möslinger D, Pasquini E, Santer R, Schwab KO, Wilcken B, Fowler B, Yue WW, Baumgartner MR.

Orphanet J Rare Dis. 2012 May 29;7:31. doi: 10.1186/1750-1172-7-31.

PubMed [citation]

PMID:: 22642865
PMCID:: PMC3495011

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000819533.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change disrupts the translational stop signal of the MCCC2 mRNA. It is expected to extend the length of the MCCC2 protein by 3 additional amino acid residues. This variant is present in population databases (rs751970792, gnomAD 0.007%). This protein extension has been observed in individual(s) with 3 Methylcrotonyl-CoA carboxylase deficiency (PMID: 16010683, 22642865; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 570791). For these reasons, this variant has been classified as 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: Apr 12, 2026

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