VCV000370039.2 - ClinVar

NM_001018005.2(TPM1):c.114+2T>C

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.

(1)

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.

Likely pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001018005.2(TPM1):c.114+2T>C

Variation ID: 370039 Accession: VCV000370039.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 15q22.2 15: 63042945 (GRCh38) [ NCBI UCSC ] 15: 63335144 (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	Jun 25, 2017	Jun 25, 2017

HGVS

Nucleotide	Protein	Molecular consequence
NM_001018005.2:c.114+2T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice donor
NM_000366.6:c.114+2T>C		splice donor
NM_001018004.2:c.114+2T>C		splice donor
NM_001018006.2:c.114+2T>C		splice donor
NM_001018007.2:c.114+2T>C		splice donor
NM_001018020.2:c.114+2T>C		splice donor
NM_001301244.2:c.114+2T>C		splice donor
NM_001365776.1:c.114+2T>C		splice donor
NM_001365777.1:c.114+2T>C		splice donor
NM_001365778.1:c.114+2T>C		splice donor
NM_001365779.1:c.114+2T>C		splice donor
NM_001407322.1:c.114+2T>C		splice donor
NM_001407323.1:c.114+2T>C		splice donor
NM_001407324.1:c.114+2T>C		splice donor
NM_001407325.1:c.114+2T>C		splice donor
NM_001407326.1:c.114+2T>C		splice donor
NM_001407327.1:c.114+2T>C		splice donor
NM_001407328.1:c.114+2T>C		splice donor
NM_001407329.1:c.114+2T>C		splice donor
NM_001407330.1:c.114+2T>C		splice donor
NM_001407331.1:c.114+2T>C		splice donor
NM_001407332.1:c.114+2T>C		splice donor
NM_001407333.1:c.114+2T>C		splice donor
NM_001407334.1:c.114+2T>C		splice donor
NM_001407335.1:c.114+2T>C		splice donor
NM_001407336.1:c.114+2T>C		splice donor
NM_001407337.1:c.114+2T>C		splice donor
NM_001407338.1:c.114+2T>C		splice donor
NC_000015.10:g.63042945T>C
NC_000015.9:g.63335144T>C
NG_007557.1:g.5307T>C
LRG_387:g.5307T>C
LRG_387t1:c.114+2T>C

... more HGVS ... less HGVS

Protein change

Other names

TPM1

Canonical SPDI

NC_000015.10:63042944:T:C

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

Variation affecting splicing function of RNA; Variation Ontology [ VariO:0397]

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.

Links

ClinGen: CA392718181 dbSNP: rs1114167357 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.
TPM1		No evidence available	No evidence available	GRCh38 GRCh37	855	903

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.
Tetralogy of Fallot	Likely pathogenic (1)	no assertion criteria provided	-	RCV000491976.2

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.
Likely pathogenic (-)	no assertion criteria provided Method: in vitro	Tetralogy of Fallot (Autosomal dominant inheritance) Affected status: not applicable Allele origin: not applicable	Laboratory of Research in Genomics, Genetics and Bioinformatics, Hospital Infantil de Mexico Federico Gomez Study: TPM1 mutations in CHD Accession: SCV000321072.1 First in ClinVar: Jun 25, 2017 Last updated: Jun 25, 2017	Publications: PubMed (1) PubMed: 28359939 Sex: female Result: Genomic DNA was obtained from patient A with a heterozygous splicing-donor site mutation at exon1-intron1 (as described above). DNA was also obtained from a control subject. PCR products were obtained and subcloned into pcDNA3.1(+) (Invitrogen). Clones were sequenced to identify a splice-site mutation, and wildtype constructs. COS7 cells were transfected with each construct using Polyfect Transfection reagent (Qiagen) and incubated for 48 h. Following RNA extraction, reverse transcription was performed using 0.5 µg of RNA per reaction. A primer pair specific to TPM1 5’ upstream and exon2a were used to detect TPM1 products. To assess the functional consequence of a novel TPM1 spice site mutation, two constructs were created, spanning the 5’ upstream region of TPM1 to exon 2a, using patient A and a control’s genomic DNA (Fig. 1E). Constructs contained either the IVS1+2T>C splice site mutation, or wild-type TPM1. RT-PCR showed that the wild-type produced a transcribed TPM1 product of 307 bp whilst no concurrent product was seen for the splice-site mutation construct .

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help 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 Help 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.
Variation affecting splicing function of RNA	Method not provided	Genomic DNA was obtained from patient A with a heterozygous splicing-donor site mutation at exon1-intron1 (as described above). DNA was also obtained from a control subject. PCR products were obtained and subcloned into pcDNA3.1(+) (Invitrogen). Clones were sequenced to identify a splice-site mutation, and wildtype constructs. COS7 cells were transfected with each construct using Polyfect Transfection reagent (Qiagen) and incubated for 48 h. Following RNA extraction, reverse transcription was performed using 0.5 µg of RNA per reaction. A primer pair specific to TPM1 5’ upstream and exon2a were used to detect TPM1 products. To assess the functional consequence of a novel TPM1 spice site mutation, two constructs were created, spanning the 5’ upstream region of TPM1 to exon 2a, using patient A and a control’s genomic DNA (Fig. 1E). Constructs contained either the IVS1+2T>C splice site mutation, or wild-type TPM1. RT-PCR showed that the wild-type produced a transcribed TPM1 product of 307 bp whilst no concurrent product was seen for the splice-site mutation construct .	Laboratory of Research in Genomics, Genetics and Bioinformatics, Hospital Infantil de Mexico Federico Gomez Study: TPM1 mutations in CHD Accession: SCV000321072.1	Publications PubMed (1)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Tropomyosin 1: Multiple roles in the developing heart and in the formation of congenital heart defects.	England J	Journal of molecular and cellular cardiology	2017	PMID: 28359939

Text-mined citations for rs1114167357 ...

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 Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_001018005.2(TPM1):c.114+2T>C

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1114167357 ...