ClinVar Genomic variation as it relates to human health
NM_001010874.5(TECRL):c.742_758del (p.Arg248fs)
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_001010874.5(TECRL):c.742_758del (p.Arg248fs)
Variation ID: 1210126 Accession: VCV001210126.1
- Type and length
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Deletion, 17 bp
- Location
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Cytogenetic: 4q13.1 4: 64299990-64300006 (GRCh38) [ NCBI UCSC ] 4: 65165708-65165724 (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 Aug 26, 2021 Aug 26, 2021 Aug 5, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001010874.5:c.742_758del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001010874.2:p.Arg248fs frameshift NM_001363796.1:c.742_758del NP_001350725.1:p.Arg248fs frameshift NC_000004.12:g.64299991_64300007del NC_000004.11:g.65165709_65165725del NG_053152.1:g.114504_114520del - Protein change
- R248fs
- Other names
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- Canonical SPDI
- NC_000004.12:64299989:GATACTGTGATTTGCCTG:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- Uncertain function
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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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- Links
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
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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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TECRL | - | - |
GRCh38 GRCh37 |
240 | 259 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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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Likely pathogenic (1) |
criteria provided, single submitter
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Aug 5, 2021 | RCV001580151.1 |
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
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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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Likely pathogenic
(Aug 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Catecholaminergic polymorphic ventricular tachycardia 3
(Autosomal recessive inheritance)
Affected status: no, yes
Allele origin:
inherited,
unknown
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Molecular and Cytogenetics Laboratory, Americain University of Beirut Medical Center
Accession: SCV001805856.1
First in ClinVar: Aug 26, 2021 Last updated: Aug 26, 2021 |
Comment:
To date, the Arg248Cysfs*8 variant in TECRL has never been reported as a pathogenic variant in the medical literature. It was detected in 2 siblings … (more)
To date, the Arg248Cysfs*8 variant in TECRL has never been reported as a pathogenic variant in the medical literature. It was detected in 2 siblings (9-year-old boy and 13-year-old girl) with a mixed phenotype of Long QT syndrome and Catecholaminergic polymorphic ventricular tachycardia (CPVT), in the context of positive family history of sudden death in their 2 siblings at a young age (the sister who has been previously healthy collapsed at the age of 16 years while climbing stairs and she could not be resuscitated. The brother who did have mild developmental delay collapsed at the age of 5 years after shocking as he went immediately flaccid without initiating reflex). No molecular or tissue autopsy done for any of the deceased victims. The variant was detected in the homozygous state in the 2 probands and in heterozygosity in each of the consanguineous parents (both asymptomatic, normal cardiac workup), suggesting an autosomal recessive inheritance. This variant creates a shift in the reading frame starting at codon 248. The new reading frame ends in a stop codon 8 positions downstream. This variant is absent in general population databases (gnomAD, 1000 Genomes Project and ExAC). Pathogenic variants in the TECRL gene are known to be associated with autosomal recessive CPVT type 3, characterized by overlapping characteristics of Long QT and CPVT (Devalla 2016, Bhuiyan 2007, Xie 2019). In summary, the Arg248Cysfs*8 variant meets the criteria to be classified as “Likely pathogenic†according to ACMG guidelines. (less)
Observation 1:
Number of individuals with the variant: 2
Clinical Features:
Syncope (present) , Ventricular tachycardia (present) , Prolonged QT interval (present) , Sudden death (present)
Age: 9-13 years
Sex: mixed
Ethnicity/Population group: white
Geographic origin: Lebanon
Comment on evidence:
2 siblings (9 year old boy and 13 year old girl) presented for cardiac evaluation in the context of 2 other siblings with sudden cardiac … (more)
2 siblings (9 year old boy and 13 year old girl) presented for cardiac evaluation in the context of 2 other siblings with sudden cardiac death. No autopsy nor genetic testing was performed for the deceased children. The ECG findings of the 2 probands showed features of mixed Long QT syndrome and CPVT, indicating a CPVT type 3. Whole exome sequencing showed homozygosity of the Arg248Cysfs*8 TECRL variant in the 2 probands, confirmed by Sanger sequencing. This variant was detected in the heterozygous state in both consanguineous parents. To note that the parents are asymptomatic and their cardiac evaluation, including exercise stress test, is normal. (less)
Testing laboratory: centogene
Date variant was reported to submitter: 2021-04-14
Testing laboratory interpretation: Uncertain significance
Observation 2:
Number of individuals with the variant: 2
Sex: mixed
Ethnicity/Population group: white
Geographic origin: Lebanon
Comment on evidence:
Non consanguineous couple, parents of 4 children of which 2 had sudden cardiac death and the other 2 presented with ECG changes suggestive of CPVT … (more)
Non consanguineous couple, parents of 4 children of which 2 had sudden cardiac death and the other 2 presented with ECG changes suggestive of CPVT type 3. Both parents are asymptomatic, with normal ECG at rest and during exercise. Both parents were found to be heterozygote for the reported variant in the TECRL gene. The affected children are homozygous for the variant. (less)
Testing laboratory: centogene
Date variant was reported to submitter: 2021-04-14
Testing laboratory interpretation: Uncertain significance
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain function
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Molecular and Cytogenetics Laboratory, Americain University of Beirut Medical Center
Accession: SCV001805856.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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A compound heterozygosity of Tecrl gene confirmed in a catecholaminergic polymorphic ventricular tachycardia family. | Xie L | European journal of medical genetics | 2019 | PMID: 30790670 |
TECRL, a new life-threatening inherited arrhythmia gene associated with overlapping clinical features of both LQTS and CPVT. | Devalla HD | EMBO molecular medicine | 2016 | PMID: 27861123 |
A novel early onset lethal form of catecholaminergic polymorphic ventricular tachycardia maps to chromosome 7p14-p22. | Bhuiyan ZA | Journal of cardiovascular electrophysiology | 2007 | PMID: 17666061 |
Text-mined citations for rs2109973501 ...
HelpRecord last updated Dec 25, 2023
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.