NM_001018005.2(TPM1):c.688G>A (p.Asp230Asn) AND Primary dilated cardiomyopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 13, 2015
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:: RCV000036354.6

Allele description [Variation Report for NM_001018005.2(TPM1):c.688G>A (p.Asp230Asn)]

NM_001018005.2(TPM1):c.688G>A (p.Asp230Asn)

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.688G>A (p.Asp230Asn)

Other names:

p.D230N:GAC>AAC

HGVS:

NC_000015.10:g.63062263G>A
NG_007557.1:g.24625G>A
NM_000366.6:c.688G>A
NM_001018004.1:c.688G>A
NM_001018004.2:c.688G>A
NM_001018005.2:c.688G>AMANE SELECT
NM_001018006.2:c.688G>A
NM_001018007.2:c.688G>A
NM_001018008.2:c.580G>A
NM_001018020.2:c.688G>A
NM_001301244.2:c.688G>A
NM_001301289.2:c.580G>A
NM_001330344.2:c.580G>A
NM_001330346.2:c.580G>A
NM_001330351.2:c.580G>A
NM_001365776.1:c.688G>A
NM_001365777.1:c.688G>A
NM_001365778.1:c.814G>A
NM_001365779.1:c.688G>A
NM_001365780.1:c.580G>A
NM_001365781.2:c.580G>A
NM_001365782.1:c.580G>A
NP_000357.3:p.Asp230Asn
NP_001018004.1:p.Asp230Asn
NP_001018005.1:p.Asp230Asn
NP_001018006.1:p.Asp230Asn
NP_001018007.1:p.Asp230Asn
NP_001018008.1:p.Asp194Asn
NP_001018020.1:p.Asp230Asn
NP_001288173.1:p.Asp230Asn
NP_001288218.1:p.Asp194Asn
NP_001317273.1:p.Asp194Asn
NP_001317275.1:p.Asp194Asn
NP_001317280.1:p.Asp194Asn
NP_001352705.1:p.Asp230Asn
NP_001352706.1:p.Asp230Asn
NP_001352707.1:p.Asp272Asn
NP_001352708.1:p.Asp230Asn
NP_001352709.1:p.Asp194Asn
NP_001352710.1:p.Asp194Asn
NP_001352711.1:p.Asp194Asn
LRG_387t1:c.688G>A
LRG_387:g.24625G>A
LRG_387p1:p.Asp230Asn
NC_000015.9:g.63354462G>A
NM_000366.5:c.688G>A
NM_001018005.1:c.688G>A
c.688G>A
p.(Asp230Asn)

Protein change:

D194N

Links:

Leiden Muscular Dystrophy (TPM1): TPM1_00015; dbSNP: rs199476317

NCBI 1000 Genomes Browser:

rs199476317

Molecular consequence:

NM_000366.6:c.688G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018004.2:c.688G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018005.2:c.688G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018006.2:c.688G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018007.2:c.688G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018008.2:c.580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018020.2:c.688G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001301244.2:c.688G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001301289.2:c.580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330344.2:c.580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330346.2:c.580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330351.2:c.580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365776.1:c.688G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365777.1:c.688G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365778.1:c.814G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365779.1:c.688G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365780.1:c.580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365781.2:c.580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365782.1:c.580G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

functional variant [Sequence Ontology: SO:0001536]

Observations:

Condition(s)

Name:: Primary dilated cardiomyopathy (DCM)
Synonyms:: Dilated Cardiomyopathy
Identifiers:: EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000060006	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Oct 13, 2015)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20117437, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000060006

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Oct 13, 2015)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	10	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

Familial dilated cardiomyopathy caused by an alpha-tropomyosin mutation: the distinctive natural history of sarcomeric dilated cardiomyopathy.

Lakdawala NK, Dellefave L, Redwood CS, Sparks E, Cirino AL, Depalma S, Colan SD, Funke B, Zimmerman RS, Robinson P, Watkins H, Seidman CE, Seidman JG, McNally EM, Ho CY.

J Am Coll Cardiol. 2010 Jan 26;55(4):320-9. doi: 10.1016/j.jacc.2009.11.017.

PubMed [citation]

PMID:: 20117437
PMCID:: PMC3000630

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000060006.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	10	not provided	not provided	clinical testing	PubMed (2)

Description

The p.Asp230Asn variant in TPM1 has been identified in 2 Caucasian individuals w ith DCM and segregated with disease in 14 affected relatives (Lakdawala 2010, LM M unpublished data). This variant was absent from large population studies. In a ddition, in vitro studies supported that this variant impacts contractility (Lak dawala 2010). In summary, the p.Asp230Asn variant meets our criteria to be class ified as pathogenic (http://pcpgm.partners.org/LMM) based on segregation and abs ence in controls.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		10	not provided	2	not provided

Last Updated: Sep 29, 2024

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