NM_001876.4(CPT1A):c.1339C>T (p.Arg447Ter) AND Carnitine palmitoyl transferase 1A deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 29, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000055854.7

Allele description [Variation Report for NM_001876.4(CPT1A):c.1339C>T (p.Arg447Ter)]

NM_001876.4(CPT1A):c.1339C>T (p.Arg447Ter)

Genes:

LOC126861244:BRD4-independent group 4 enhancer GRCh37_chr11:68549035-68550234 [Gene]
CPT1A:carnitine palmitoyltransferase 1A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.3

Genomic location:

Preferred name:

NM_001876.4(CPT1A):c.1339C>T (p.Arg447Ter)

HGVS:

NC_000011.10:g.68781784G>A
NG_011801.1:g.65148C>T
NM_001031847.3:c.1339C>T
NM_001876.4:c.1339C>TMANE SELECT
NP_001027017.1:p.Arg447Ter
NP_001867.2:p.Arg447Ter
NC_000011.9:g.68549252G>A

Protein change:

R447*

Links:

dbSNP: rs397515543

NCBI 1000 Genomes Browser:

rs397515543

Molecular consequence:

NM_001031847.3:c.1339C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001876.4:c.1339C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Carnitine palmitoyl transferase 1A deficiency
Synonyms:: Carnitine palmitoyl transferase 1 deficiency; Carnitine palmitoyltransferase 1A deficiency; CPT1A deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009705; MedGen: C1829703; Orphanet: 156; OMIM: 255120

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002242715	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 24, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19345525, 16169268, 28492532
SCV004210998	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 29, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002242715

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 24, 2023)

germline

clinical testing

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

SCV004210998

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 29, 2023)

unknown

clinical testing

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

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular analysis of a presymptomatic case of carnitine palmitoyl transferase I (CPT I) deficiency detected by tandem mass spectrometry newborn screening in Japan.

Tsuburaya R, Sakamoto O, Arai N, Kobayashi H, Hasegawa Y, Yamaguchi S, Shigematsu Y, Takayanagi M, Ohura T, Tsuchiya S.

Brain Dev. 2010 May;32(5):409-11. doi: 10.1016/j.braindev.2009.03.004. Epub 2009 Apr 3.

PubMed [citation]

PMID:: 19345525

Homozygous carnitine palmitoyltransferase 1a (liver isoform) deficiency is lethal in the mouse.

Nyman LR, Cox KB, Hoppel CL, Kerner J, Barnoski BL, Hamm DA, Tian L, Schoeb TR, Wood PA.

Mol Genet Metab. 2005 Sep-Oct;86(1-2):179-87.

PubMed [citation]

PMID:: 16169268

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002242715.3

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 65641). This variant is also known as p.R446X. This premature translational stop signal has been observed in individual(s) with carnitine palmitoyl transferase I deficiency (PMID: 19345525). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg447*) in the CPT1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CPT1A are known to be pathogenic (PMID: 16169268).

#	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 Baylor Genetics, SCV004210998.1

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

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

Last Updated: Feb 14, 2024

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