VCV000460433.20 - ClinVar

NM_000098.3(CPT2):c.236A>C (p.Lys79Thr)

Germline

Classification

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.

(14)

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.

Uncertain significance

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000098.3(CPT2):c.236A>C (p.Lys79Thr)

Variation ID: 460433 Accession: VCV000460433.20

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1p32.3 1: 53202325 (GRCh38) [ NCBI UCSC ] 1: 53667997 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	May 12, 2018	Sep 29, 2024	Feb 23, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000098.3:c.236A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000089.1:p.Lys79Thr	missense
NM_001330589.2:c.236A>C	NP_001317518.1:p.Lys79Thr	missense
NC_000001.11:g.53202325A>C
NC_000001.10:g.53667997A>C
NG_008035.1:g.10897A>C

... more HGVS ... less HGVS

Protein change

K79T

Other names

Canonical SPDI

NC_000001.11:53202324:A:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015

Exome Aggregation Consortium (ExAC) 0.00026

The Genome Aggregation Database (gnomAD) 0.00027

The Genome Aggregation Database (gnomAD), exomes 0.00027

Trans-Omics for Precision Medicine (TOPMed) 0.00031

Links

ClinGen: CA858937 dbSNP: rs150888506 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help 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 Help 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.
CPT2		-	-	GRCh38 GRCh37	899	1027

Conditions - Germline

Condition Help 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 Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Carnitine palmitoyltransferase II deficiency	Uncertain significance (3)	criteria provided, multiple submitters, no conflicts	Oct 17, 2022	RCV000530003.11
Generalized hypotonia Genu valgum Hyperextensibility at elbow Hyperextensibility of the finger joints Hyperextensible hand joints Myopathic facies Pes planus	Uncertain significance (1)	criteria provided, single submitter	Jan 1, 2017	RCV000626610.2
Carnitine palmitoyl transferase II deficiency, severe infantile form	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Apr 11, 2023	RCV001449651.2
not provided	Uncertain significance (3)	criteria provided, multiple submitters, no conflicts	Feb 23, 2024	RCV001571245.9
Carnitine palmitoyl transferase II deficiency, neonatal form	Uncertain significance (1)	criteria provided, single submitter	Apr 11, 2023	RCV003451159.1
Encephalopathy, acute, infection-induced, susceptibility to, 4	Uncertain significance (1)	criteria provided, single submitter	Apr 11, 2023	RCV003456089.1
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Oct 26, 2023	RCV004023832.1
CPT2-related disorder	Uncertain significance (1)	criteria provided, single submitter	Nov 10, 2022	RCV003403273.4
Carnitine palmitoyl transferase II deficiency, myopathic form	Uncertain significance (1)	criteria provided, single submitter	Apr 11, 2023	RCV003451158.1

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.
Uncertain significance (Jan 01, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Generalized hypotonia Genu valgum Hyperextensibility at elbow Hyperextensibility of the finger joints Hyperextensible hand joints Myopathic facies Pes planus Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV000747311.1 First in ClinVar: May 12, 2018 Last updated: May 12, 2018
Uncertain significance (Apr 28, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Carnitine palmitoyltransferase II deficiency Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001252951.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
Uncertain significance (May 18, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Carnitine palmitoyl transferase II deficiency, severe infantile form Affected status: no Allele origin: germline	Pars Genome Lab Accession: SCV001652852.1 First in ClinVar: May 29, 2021 Last updated: May 29, 2021	Sex: mixed
Uncertain significance (Oct 17, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Carnitine palmitoyltransferase II deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000632603.5 First in ClinVar: Dec 26, 2017 Last updated: Feb 07, 2023	Comment: This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 79 of the CPT2 protein (p.Lys79Thr). … (more) This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 79 of the CPT2 protein (p.Lys79Thr). This variant is present in population databases (rs150888506, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with CPT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 460433). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Uncertain significance (Nov 10, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	CPT2-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004106040.1 First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023	Comment: The CPT2 c.236A>C variant is predicted to result in the amino acid substitution p.Lys79Thr. To our knowledge, this variant has not been reported in the … (more) The CPT2 c.236A>C variant is predicted to result in the amino acid substitution p.Lys79Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.096% of alleles in individuals of Ashkenazi Jewish descent and 0.043% in in individuals of Non-Finnish European descent in gnomAD, including one homozygous individual (http://gnomad.broadinstitute.org/variant/1-53667997-A-C), which may be too common to be an unreported disease-causing variant. Although we suspect that this variant may be benign, at this time its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence. (less)
Uncertain significance (Apr 11, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Encephalopathy, acute, infection-induced, susceptibility to, 4 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV004179294.1 First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023
Uncertain significance (Apr 11, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Carnitine palmitoyl transferase II deficiency, severe infantile form Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV004179295.1 First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023
Uncertain significance (Apr 11, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Carnitine palmitoyl transferase II deficiency, neonatal form Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV004179296.1 First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023
Uncertain significance (Apr 11, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Carnitine palmitoyl transferase II deficiency, myopathic form Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV004179297.1 First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023
Uncertain significance (Jul 07, 2023)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Athena Diagnostics Accession: SCV004229556.1 First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024	Comment: Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is … (more) Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools predict that this variant is not damaging. (less)
Uncertain significance (May 31, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV003829976.2 First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024
Uncertain significance (Oct 26, 2023)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV004849785.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Comment: The c.236A>C (p.K79T) alteration is located in exon 3 (coding exon 3) of the CPT2 gene. This alteration results from a A to C substitution … (more) The c.236A>C (p.K79T) alteration is located in exon 3 (coding exon 3) of the CPT2 gene. This alteration results from a A to C substitution at nucleotide position 236, causing the lysine (K) at amino acid position 79 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
Uncertain significance (Feb 23, 2024)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001795677.2 First in ClinVar: Aug 21, 2021 Last updated: Sep 29, 2024	Comment: In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; … (more) In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29429925, 27467583, 28404951, 27460824) (less)
Uncertain significance (Jan 27, 2020)	no assertion criteria provided Method: clinical testing	Carnitine palmitoyltransferase II deficiency Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001454115.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
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Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

Comment:

This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 79 of the CPT2 protein (p.Lys79Thr). This variant is present in population databases (rs150888506, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with CPT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 460433). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Comment:

The CPT2 c.236A>C variant is predicted to result in the amino acid substitution p.Lys79Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.096% of alleles in individuals of Ashkenazi Jewish descent and 0.043% in in individuals of Non-Finnish European descent in gnomAD, including one homozygous individual (http://gnomad.broadinstitute.org/variant/1-53667997-A-C), which may be too common to be an unreported disease-causing variant. Although we suspect that this variant may be benign, at this time its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence.

Comment:

Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools predict that this variant is not damaging.

Comment:

The c.236A>C (p.K79T) alteration is located in exon 3 (coding exon 3) of the CPT2 gene. This alteration results from a A to C substitution at nucleotide position 236, causing the lysine (K) at amino acid position 79 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Comment:

In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29429925, 27467583, 28404951, 27460824)

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.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs150888506 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 08, 2024

ClinVar Genomic variation as it relates to human health

NM_000098.3(CPT2):c.236A>C (p.Lys79Thr)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs150888506 ...