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NM_001018005.2(TPM1):c.275T>C (p.Ile92Thr) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 6, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV002433467.3

Allele description [Variation Report for NM_001018005.2(TPM1):c.275T>C (p.Ile92Thr)]

NM_001018005.2(TPM1):c.275T>C (p.Ile92Thr)

Gene:
TPM1:tropomyosin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q22.2
Genomic location:
Preferred name:
NM_001018005.2(TPM1):c.275T>C (p.Ile92Thr)
HGVS:
  • NC_000015.10:g.63057019T>C
  • NG_007557.1:g.19381T>C
  • NM_000366.6:c.275T>C
  • NM_001018004.2:c.275T>C
  • NM_001018005.2:c.275T>CMANE SELECT
  • NM_001018006.2:c.275T>C
  • NM_001018007.2:c.275T>C
  • NM_001018008.2:c.167T>C
  • NM_001018020.2:c.275T>C
  • NM_001301244.2:c.275T>C
  • NM_001301289.2:c.167T>C
  • NM_001330344.2:c.167T>C
  • NM_001330346.2:c.167T>C
  • NM_001330351.2:c.167T>C
  • NM_001365776.1:c.275T>C
  • NM_001365777.1:c.275T>C
  • NM_001365778.1:c.401T>C
  • NM_001365779.1:c.275T>C
  • NM_001365780.1:c.167T>C
  • NM_001365781.2:c.167T>C
  • NM_001365782.1:c.167T>C
  • NP_000357.3:p.Ile92Thr
  • NP_001018004.1:p.Ile92Thr
  • NP_001018005.1:p.Ile92Thr
  • NP_001018006.1:p.Ile92Thr
  • NP_001018007.1:p.Ile92Thr
  • NP_001018008.1:p.Ile56Thr
  • NP_001018020.1:p.Ile92Thr
  • NP_001288173.1:p.Ile92Thr
  • NP_001288218.1:p.Ile56Thr
  • NP_001317273.1:p.Ile56Thr
  • NP_001317275.1:p.Ile56Thr
  • NP_001317280.1:p.Ile56Thr
  • NP_001352705.1:p.Ile92Thr
  • NP_001352706.1:p.Ile92Thr
  • NP_001352707.1:p.Ile134Thr
  • NP_001352708.1:p.Ile92Thr
  • NP_001352709.1:p.Ile56Thr
  • NP_001352710.1:p.Ile56Thr
  • NP_001352711.1:p.Ile56Thr
  • LRG_387t1:c.275T>C
  • LRG_387:g.19381T>C
  • LRG_387p1:p.Ile92Thr
  • NC_000015.9:g.63349218T>C
  • NM_000366.5:c.275T>C
  • NM_001018005.1:c.275T>C
  • c.275T>C
  • p.(Ile92Thr)
Protein change:
I134T
Links:
Leiden Muscular Dystrophy (TPM1): TPM1_00022; dbSNP: rs199476310
NCBI 1000 Genomes Browser:
rs199476310
Molecular consequence:
  • NM_000366.6:c.275T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018004.2:c.275T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018005.2:c.275T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018006.2:c.275T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018007.2:c.275T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018008.2:c.167T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018020.2:c.275T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301244.2:c.275T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301289.2:c.167T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330344.2:c.167T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330346.2:c.167T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330351.2:c.167T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365776.1:c.275T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365777.1:c.275T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365778.1:c.401T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365779.1:c.275T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365780.1:c.167T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365781.2:c.167T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365782.1:c.167T>C - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
functional variant [Sequence Ontology: SO:0001536]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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  • RecName: Full=Tumor necrosis factor ligand superfamily member 6; AltName: Full=C...
    RecName: Full=Tumor necrosis factor ligand superfamily member 6; AltName: Full=CD95 ligand; Short=CD95-L; AltName: Full=Fas antigen ligand; Short=Fas ligand; Short=FasL; AltName: CD_antigen=CD178; Contains: RecName: Full=Tumor necrosis factor ligand superfamily member 6, membrane form; Contains: RecName: Full=Tumor necrosis factor ligand superfamily member 6, soluble form; AltName: Full=Receptor-binding FasL ectodomain; AltName: Full=Soluble Fas ligand; Short=sFasL; Contains: RecName: Full=ADAM10-processed FasL form; Short=APL; Contains: RecName: Full=FasL intracellular domain; Short=FasL ICD; AltName: Full=SPPL2A-processed FasL form; Short=SPA
    gi|729462|sp|P41047.1|TNFL6_MOUSE
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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002752017Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Sep 6, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy.

Hershberger RE, Norton N, Morales A, Li D, Siegfried JD, Gonzalez-Quintana J.

Circ Cardiovasc Genet. 2010 Apr;3(2):155-61. doi: 10.1161/CIRCGENETICS.109.912345. Epub 2010 Mar 9.

PubMed [citation]
PMID:
20215591
PMCID:
PMC2908892

Rare variant mutations identified in pediatric patients with dilated cardiomyopathy.

Rampersaud E, Siegfried JD, Norton N, Li D, Martin E, Hershberger RE.

Prog Pediatr Cardiol. 2011 Jan 1;31(1):39-47.

PubMed [citation]
PMID:
21483645
PMCID:
PMC3072577
See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV002752017.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

The p.I92T variant (also known as c.275T>C), located in coding exon 3 of the TPM1 gene, results from a T to C substitution at nucleotide position 275. The isoleucine at codon 92 is replaced by threonine, an amino acid with similar properties. This variant has been detected in identical twins with pediatric-onset dilated cardiomyopathy (DCM), and was also detected in relatives reported to have DCM (Hershberger RE et al. Circ Cardiovasc Genet, 2010 Apr;3:155-61;Rampersaud E et al. Prog. Pediatr. Cardiol., 2011 Jan;31:39-47). This variant has also been reported in cohorts referred for DCM genetic testing; however, details were limited and reports may overlap (Walsh R et al. Genet. Med., 2017 02;19:192-203; Pugh TJ et al. Genet. Med., 2014 Aug;16:601-8). One study reported this variant may impact protein function (liwinska M et al. Biochim Biophys Acta Proteins Proteom, 2018 Apr;1866:558-568). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024