NM_001876.4(CPT1A):c.1069C>T (p.Arg357Trp) AND Carnitine palmitoyl transferase 1A deficiency

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Mar 23, 2024
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:: RCV000055853.10

Allele description [Variation Report for NM_001876.4(CPT1A):c.1069C>T (p.Arg357Trp)]

NM_001876.4(CPT1A):c.1069C>T (p.Arg357Trp)

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.1069C>T (p.Arg357Trp)

HGVS:

NC_000011.10:g.68784909G>A
NG_011801.1:g.62023C>T
NM_001031847.3:c.1069C>T
NM_001876.4:c.1069C>TMANE SELECT
NP_001027017.1:p.Arg357Trp
NP_001867.2:p.Arg357Trp
NC_000011.9:g.68552377G>A
NM_001876.3:c.1069C>T
P50416:p.Arg357Trp

Protein change:

R357W

Links:

UniProtKB: P50416#VAR_020550; dbSNP: rs80356777

NCBI 1000 Genomes Browser:

rs80356777

Molecular consequence:

NM_001031847.3:c.1069C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001876.4:c.1069C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000086849	GeneReviews	no classification provided	not provided	germline	literature only
SCV002261269	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 27, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11441142, 28492532
SCV004211011	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 23, 2024)	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

SCV000086849

GeneReviews

no classification provided

not provided

germline

literature only

SCV002261269

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 27, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004211011

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 23, 2024)

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, literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular characterization of L-CPT I deficiency in six patients: insights into function of the native enzyme.

Brown NF, Mullur RS, Subramanian I, Esser V, Bennett MJ, Saudubray JM, Feigenbaum AS, Kobari JA, Macleod PM, McGarry JD, Cohen JC.

J Lipid Res. 2001 Jul;42(7):1134-42.

PubMed [citation]

PMID:: 11441142

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From GeneReviews, SCV000086849.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002261269.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is present in population databases (rs80356777, gnomAD 0.005%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 357 of the CPT1A protein (p.Arg357Trp). This missense change has been observed in individual(s) with CPT1 deficiency (PMID: 11441142). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects CPT1A function (PMID: 11441142). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CPT1A protein function. ClinVar contains an entry for this variant (Variation ID: 65640).

#	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, SCV004211011.2

#	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: Sep 29, 2024

ClinVar

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