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NM_001018005.2(TPM1):c.574G>A (p.Glu192Lys) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 13, 2022
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:
RCV002345253.1

Allele description

NM_001018005.2(TPM1):c.574G>A (p.Glu192Lys)

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.574G>A (p.Glu192Lys)
Other names:
p.E192K:GAG>AAG
HGVS:
  • NC_000015.10:g.63061723G>A
  • NG_007557.1:g.24085G>A
  • NM_000366.6:c.639+450G>A
  • NM_001018004.2:c.574G>A
  • NM_001018005.2:c.574G>AMANE SELECT
  • NM_001018006.2:c.639+450G>A
  • NM_001018007.2:c.574G>A
  • NM_001018008.2:c.466G>A
  • NM_001018020.2:c.639+450G>A
  • NM_001301244.2:c.574G>A
  • NM_001301289.2:c.466G>A
  • NM_001330344.2:c.531+450G>A
  • NM_001330346.2:c.466G>A
  • NM_001330351.2:c.531+450G>A
  • NM_001365776.1:c.574G>A
  • NM_001365777.1:c.574G>A
  • NM_001365778.1:c.700G>A
  • NM_001365779.1:c.574G>A
  • NM_001365780.1:c.466G>A
  • NM_001365781.2:c.531+450G>A
  • NM_001365782.1:c.466G>A
  • NP_001018004.1:p.Glu192Lys
  • NP_001018005.1:p.Glu192Lys
  • NP_001018007.1:p.Glu192Lys
  • NP_001018008.1:p.Glu156Lys
  • NP_001288173.1:p.Glu192Lys
  • NP_001288218.1:p.Glu156Lys
  • NP_001317275.1:p.Glu156Lys
  • NP_001352705.1:p.Glu192Lys
  • NP_001352706.1:p.Glu192Lys
  • NP_001352707.1:p.Glu234Lys
  • NP_001352708.1:p.Glu192Lys
  • NP_001352709.1:p.Glu156Lys
  • NP_001352711.1:p.Glu156Lys
  • LRG_387t1:c.574G>A
  • LRG_387:g.24085G>A
  • LRG_387p1:p.Glu192Lys
  • NC_000015.9:g.63353922G>A
  • NM_001018005.1:c.574G>A
  • NM_001018005.2:c.574G>A
  • NM_001018020.1:c.639+450G>A
  • P09493:p.Glu192Lys
  • c.574G>A
  • p.(Glu192Lys)
Protein change:
E156K; GLU192LYS
Links:
Leiden Muscular Dystrophy (TPM1): TPM1_00013; UniProtKB: P09493#VAR_070121; OMIM: 191010.0007; dbSNP: rs199476315
NCBI 1000 Genomes Browser:
rs199476315
Molecular consequence:
  • NM_000366.6:c.639+450G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001018006.2:c.639+450G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001018020.2:c.639+450G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001330344.2:c.531+450G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001330351.2:c.531+450G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001365781.2:c.531+450G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001018004.2:c.574G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018005.2:c.574G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018007.2:c.574G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018008.2:c.466G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301244.2:c.574G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301289.2:c.466G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330346.2:c.466G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365776.1:c.574G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365777.1:c.574G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365778.1:c.700G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365779.1:c.574G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365780.1:c.466G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365782.1:c.466G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
functional variant [Sequence Ontology: SO:0001536]
Observations:
1

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002651645Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Pathogenic
(Jul 13, 2022) 		germlineclinical testing

PubMed (17)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

A DNA resequencing array for pathogenic mutation detection in hypertrophic cardiomyopathy.

Fokstuen S, Lyle R, Munoz A, Gehrig C, Lerch R, Perrot A, Osterziel KJ, Geier C, Beghetti M, Mach F, Sztajzel J, Sigwart U, Antonarakis SE, Blouin JL.

Hum Mutat. 2008 Jun;29(6):879-85. doi: 10.1002/humu.20749.

PubMed [citation]
PMID:
18409188

Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy.

Ho CY, Carlsen C, Thune JJ, Havndrup O, Bundgaard H, Farrohi F, Rivero J, Cirino AL, Andersen PS, Christiansen M, Maron BJ, Orav EJ, Køber L.

Circ Cardiovasc Genet. 2009 Aug;2(4):314-21. doi: 10.1161/CIRCGENETICS.109.862128. Epub 2009 Jun 19.

PubMed [citation]
PMID:
20031602
PMCID:
PMC2773504
See all PubMed Citations (17)

Details of each submission

From Ambry Genetics, SCV002651645.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (17)

Description

The p.E192K pathogenic mutation (also known as c.574G>A), located in coding exon 6 of the TPM1 gene, results from a G to A substitution at nucleotide position 574. The glutamic acid at codon 192 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in numerous individuals with hypertrophic cardiomyopathy (HCM) and was shown to co-segregate with disease in one family (Deva DP et al. Radiology. 2013;269:68-76; Coppini R et al. J. Am. Coll. Cardiol. 2014;64:2589-2600; Kapplinger JD et al. J Cardiovasc Transl Res. 2014;7:347-61; Lopes LR et al. Heart. 2015;101:294-301; Mango R et al. Circ. J. 2016;80:938-49; Ross SB et al. Circ Cardiovasc Genet. 2017;10(3):e001671; Walsh R et al. Genet. Med. 2017;19:192-203). This variant has also been detected in one patient with left ventricular noncompaction (LVNC) (Probst S et al. Circ Cardiovasc Genet. 2011;4:367-74). This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by BayesDel in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Mar 16, 2024