NM_001876.4(CPT1A):c.100T>C (p.Ser34Pro) AND Carnitine palmitoyl transferase 1A deficiency

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Aug 31, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000693588.21

Allele description

NM_001876.4(CPT1A):c.100T>C (p.Ser34Pro)

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.100T>C (p.Ser34Pro)

HGVS:

NC_000011.10:g.68815375A>G
NG_011801.1:g.31557T>C
NM_001031847.3:c.100T>C
NM_001876.4:c.100T>CMANE SELECT
NP_001027017.1:p.Ser34Pro
NP_001867.2:p.Ser34Pro
NC_000011.9:g.68582843A>G
NM_001876.3:c.100T>C

Protein change:

S34P

Links:

dbSNP: rs398123653

NCBI 1000 Genomes Browser:

rs398123653

Molecular consequence:

NM_001031847.3:c.100T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001876.4:c.100T>C - 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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AL630832 XGC-gastrula Xenopus tropicalis cDNA clone TGas014g16 5', mRNA sequence
AL630832 XGC-gastrula Xenopus tropicalis cDNA clone TGas014g16 5', mRNA sequence
gi|38450169|gnl|dbEST|20479126|emb| 832.2|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000821463	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 31, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000894655	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 31, 2018)	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

SCV000821463

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 31, 2023)

germline

clinical testing

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

SCV000894655

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 31, 2018)

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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

PMC

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From Invitae, SCV000821463.7

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

Description

This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 34 of the CPT1A protein (p.Ser34Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with CPT1A-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 93971). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant disrupts the p.Ser34 amino acid residue in CPT1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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

From Fulgent Genetics, Fulgent Genetics, SCV000894655.1

#	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: Sep 16, 2024

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