ClinVar Genomic variation as it relates to human health
NM_000098.3(CPT2):c.1239_1240del (p.Lys414fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000098.3(CPT2):c.1239_1240del (p.Lys414fs)
Variation ID: 92430 Accession: VCV000092430.80
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 1p32.3 1: 53210912-53210913 (GRCh38) [ NCBI UCSC ] 1: 53676584-53676585 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 21, 2015 May 12, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000098.3:c.1239_1240del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000089.1:p.Lys414fs frameshift NM_000098.3:c.1239_1240delGA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000098.2:c.1238_1239del NM_000098.2:c.1239_1240delGA NM_001330589.2:c.1239_1240del NP_001317518.1:p.Lys414fs frameshift NC_000001.11:g.53210913_53210914del NC_000001.10:g.53676585_53676586del NG_008035.1:g.19485_19486del - Protein change
- K414fs
- Other names
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- Canonical SPDI
- NC_000001.11:53210911:AGA:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CPT2 | - | - |
GRCh38 GRCh37 |
886 | 1013 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Aug 29, 2023 | RCV000185837.33 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV000202516.23 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Apr 11, 2023 | RCV000576522.13 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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May 6, 2021 | RCV002225079.11 | |
Pathogenic (1) |
criteria provided, single submitter
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May 3, 2022 | RCV002490673.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 29, 2023 | RCV003474675.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jul 25, 2012)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000109955.8
First in ClinVar: Jan 17, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 5
Sex: mixed
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Pathogenic
(May 06, 2021)
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criteria provided, single submitter
Method: clinical testing
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Carnitine palmitoyl transferase II deficiency, myopathic form
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002767254.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with neonatal, infantile and stress-induced myopathic CPT II deficiency. (I) 0106 - This gene is associated with autosomal recessive disease. This gene is generally considered to be associated with an autosomal recessive condition, but some cases of manifesting carriers have been reported for the myopathic of CPT II deficiency (PMID: 32295037). (I) 0115 - Variants in this gene are known to have variable expressivity. The myopathic form of this condition can manifest from infancy to adulthood and variable onset, frequency, and severity of symptoms have been reported (PMID: 32295037). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2) (53 heterozygotes, 0 homozygotes) and is enriched in the Ashkenazi Jewish sub-population. (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Other variants predicted to cause NMD have been reported as pathogenic in individuals with CPT II deficiency (ClinVar). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in multiple individuals with the myopathic form of CPT II deficiency (ClinVar, PMID: 21913903). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Pathogenic
(May 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Carnitine palmitoyl transferase II deficiency, myopathic form
Carnitine palmitoyl transferase II deficiency, severe infantile form Carnitine palmitoyl transferase II deficiency, neonatal form Encephalopathy, acute, infection-induced, susceptibility to, 4
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002780858.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Aug 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000238786.11
First in ClinVar: Jul 18, 2015 Last updated: Sep 07, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Also … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Also known as 413delAG, 1237delAG and c.del1238_1239AG; This variant is associated with the following publications: (PMID: 22975760, 25827434, 19335026, 28871440, 34958143, 31428121, 11477613, 10090476) (less)
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Pathogenic
(Oct 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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Encephalopathy, acute, infection-induced, susceptibility to, 4
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004211028.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Apr 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001335204.20
First in ClinVar: Jun 08, 2020 Last updated: May 12, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Jun 10, 2016)
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criteria provided, single submitter
Method: clinical testing
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Carnitine palmitoyltransferase II deficiency
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695404.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Comment:
Variant summary: The CPT2 c.1239_1240delGA (p.Lys414Thrfs) variant results in a premature termination codon, predicted to cause a truncated or absent CPT2 protein due to nonsense … (more)
Variant summary: The CPT2 c.1239_1240delGA (p.Lys414Thrfs) variant results in a premature termination codon, predicted to cause a truncated or absent CPT2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 13/121214 (1/9328), which does not exceed the estimated maximal expected allele frequency for a pathogenic CPT2 variant of 1/9328 (0.0015811). The variant of interest has been reported in multiple affected individuals via publications and has been indicated to be a part of a complex allele with another pathogenic CPT2 variant, p.F448L in multiple affected individuals. In addition, multiple clinical laboratories/databases cite the variant as "pathogenic." Therefore, taking all available lines of evidence, the variant of interest is classified as Pathogenic. (less)
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Pathogenic
(Dec 19, 2019)
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criteria provided, single submitter
Method: clinical testing
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Carnitine palmitoyl transferase II deficiency, severe infantile form
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV001194174.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 06, 2020 |
Comment:
NM_000098.2(CPT2):c.1239_1240delGA(K414Tfs*7) is classified as pathogenic in the context of carnitine palmitoyltransferase II deficiency and is associated with the neonatal form of disease. Sources cited for … (more)
NM_000098.2(CPT2):c.1239_1240delGA(K414Tfs*7) is classified as pathogenic in the context of carnitine palmitoyltransferase II deficiency and is associated with the neonatal form of disease. Sources cited for classification include the following: PMID 12673791, 16996287, 10090476‚Äé, 18550408 and 15642848. Classification of NM_000098.2(CPT2):c.1239_1240delGA(K414Tfs*7) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening. (less)
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Pathogenic
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Carnitine palmitoyl transferase II deficiency, severe infantile form
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV004179492.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
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Pathogenic
(Oct 21, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002019725.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Carnitine palmitoyltransferase II deficiency
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000632584.9
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Lys414Thrfs*7) in the CPT2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Lys414Thrfs*7) in the CPT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CPT2 are known to be pathogenic (PMID: 16781677, 16996287). This variant is present in population databases (rs397509431, gnomAD 0.5%). This premature translational stop signal has been observed in individual(s) with CPT2-deficiency, and has been observed to occur in cis with the p.Phe448Leu missense change (PMID: 10090476, 12673791, 12707442, 21913903). This variant is also known as c.del1238_1239AG/Q413fs. ClinVar contains an entry for this variant (Variation ID: 92430). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Oct 26, 2020)
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criteria provided, single submitter
Method: clinical testing
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Carnitine palmitoyl transferase II deficiency, myopathic form
Affected status: yes
Allele origin:
germline
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Molecular Genetics, Royal Melbourne Hospital
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002503836.2
First in ClinVar: Apr 30, 2022 Last updated: Apr 15, 2024 |
Comment:
This sequence change is a deletion of 2 bp in exon 4 (of 5) of CPT2 that is predicted to create a premature termination codon … (more)
This sequence change is a deletion of 2 bp in exon 4 (of 5) of CPT2 that is predicted to create a premature termination codon at position 420 (p.(Lys414Thrfs*7)). It is expected to result in nonsense mediated decay, in a gene where loss of function is an established mechanism of disease (ClinVar). The variant is present in a large population cohort at a frequency of 0.02%, which is consistent with recessive disease (rs397509431, 53/251,372 alleles, 0 homozygotes in gnomAD v2.1). It is more common in the Ashkenazi Jewish population at a frequency of 0.5% (47/10,080 alleles in gnomAD v2.1). The variant is the second most commonly occurring pathogenic variant in Europeans, always in cis with NM_000098.3:c.1342T>C, p.Phe448Leu (PMID: 20301431). The variant has been identified in the homozygous state and with a second pathogenic allele in multiple cases with phenotypes ranging from the lethal neonatal, infantile, and myopathic forms of CPT II deficiency, and segregates with disease in at least one family (PMID: 10090476, 11477613, 12410208). CPT II deficiency has been demonstrated in patient cells from homozygous cases, including both enzyme activity and long-chain fatty-acid oxidation (PMID: 11477613). Based on the classification scheme RMH ACMG Guidelines v1.2.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM3_VeryStrong, PM2, PP1, PP4. (less)
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Carnitine palmitoyltransferase II deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001454238.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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not provided
(-)
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no classification provided
Method: literature only
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Carnitine palmitoyltransferase II deficiency
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000153665.3
First in ClinVar: Dec 21, 2015 Last updated: Oct 01, 2022 |
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not provided
(-)
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no classification provided
Method: phenotyping only
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Carnitine palmitoyltransferase II deficiency
Affected status: unknown
Allele origin:
unknown
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GenomeConnect - Invitae Patient Insights Network
Accession: SCV004228577.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
Variant interpreted as Pathogenic and reported on 06-11-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpreted as Pathogenic and reported on 06-11-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Clinical Features:
Abnormal muscle physiology (present)
Indication for testing: Presymptomatic, Family Testing
Age: 50-59 years
Sex: male
Method: Familial/Targeted Variant Analysis
Testing laboratory: Invitae
Date variant was reported to submitter: 2019-06-11
Testing laboratory interpretation: Pathogenic
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Muscle Carnitine Palmitoyltransferase II (CPT II) Deficiency: A Conceptual Approach. | Joshi PR | Molecules (Basel, Switzerland) | 2020 | PMID: 32295037 |
Carnitine Palmitoyltransferase II Deficiency. | Adam MP | - | 2019 | PMID: 20301431 |
Allelic and phenotypic heterogeneity in 49 Italian patients with the muscle form of CPT-II deficiency. | Fanin M | Clinical genetics | 2012 | PMID: 21913903 |
CPT2 gene mutations resulting in lethal neonatal or severe infantile carnitine palmitoyltransferase II deficiency. | Isackson PJ | Molecular genetics and metabolism | 2008 | PMID: 18550408 |
Identification of 16 new disease-causing mutations in the CPT2 gene resulting in carnitine palmitoyltransferase II deficiency. | Isackson PJ | Molecular genetics and metabolism | 2006 | PMID: 16996287 |
Crystal structure of rat carnitine palmitoyltransferase II (CPT-II). | Hsiao YS | Biochemical and biophysical research communications | 2006 | PMID: 16781677 |
Muscle carnitine palmitoyltransferase II deficiency: clinical and molecular genetic features and diagnostic aspects. | Deschauer M | Archives of neurology | 2005 | PMID: 15642848 |
Carnitine palmitoyltransferase II deficiency: molecular and biochemical analysis of 32 patients. | Wieser T | Neurology | 2003 | PMID: 12707442 |
Correlation between genotype, metabolic data, and clinical presentation in carnitine palmitoyltransferase 2 (CPT2) deficiency. | Thuillier L | Human mutation | 2003 | PMID: 12673791 |
Lethal neonatal and severe late infantile forms of carnitine palmitoyltransferase II deficiency associated with compound heterozygosity for different protein truncation mutations. | Vladutiu GD | The Journal of pediatrics | 2002 | PMID: 12410208 |
Antenatal presentation of carnitine palmitoyltransferase II deficiency. | Elpeleg ON | American journal of medical genetics | 2001 | PMID: 11477613 |
Novel mutations associated with carnitine palmitoyltransferase II deficiency. | Taggart RT | Human mutation | 1999 | PMID: 10090476 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CPT2 | - | - | - | - |
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Text-mined citations for rs397509431 ...
HelpRecord last updated May 12, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.