NM_001018005.2(TPM1):c.715G>A (p.Ala239Thr) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 16, 2018
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:: RCV000471524.6

Allele description [Variation Report for NM_001018005.2(TPM1):c.715G>A (p.Ala239Thr)]

NM_001018005.2(TPM1):c.715G>A (p.Ala239Thr)

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.715G>A (p.Ala239Thr)

HGVS:

NC_000015.10:g.63062588G>A
NG_007557.1:g.24950G>A
NM_000366.6:c.715G>A
NM_001018004.2:c.715G>A
NM_001018005.2:c.715G>AMANE SELECT
NM_001018006.2:c.715G>A
NM_001018007.2:c.715G>A
NM_001018008.2:c.607G>A
NM_001018020.2:c.715G>A
NM_001301244.2:c.715G>A
NM_001301289.2:c.607G>A
NM_001330344.2:c.607G>A
NM_001330346.2:c.607G>A
NM_001330351.2:c.607G>A
NM_001365776.1:c.715G>A
NM_001365777.1:c.715G>A
NM_001365778.1:c.841G>A
NM_001365779.1:c.715G>A
NM_001365780.1:c.607G>A
NM_001365781.2:c.607G>A
NM_001365782.1:c.607G>A
NP_000357.3:p.Ala239Thr
NP_001018004.1:p.Ala239Thr
NP_001018005.1:p.Ala239Thr
NP_001018006.1:p.Ala239Thr
NP_001018007.1:p.Ala239Thr
NP_001018008.1:p.Ala203Thr
NP_001018020.1:p.Ala239Thr
NP_001288173.1:p.Ala239Thr
NP_001288218.1:p.Ala203Thr
NP_001317273.1:p.Ala203Thr
NP_001317275.1:p.Ala203Thr
NP_001317280.1:p.Ala203Thr
NP_001352705.1:p.Ala239Thr
NP_001352706.1:p.Ala239Thr
NP_001352707.1:p.Ala281Thr
NP_001352708.1:p.Ala239Thr
NP_001352709.1:p.Ala203Thr
NP_001352710.1:p.Ala203Thr
NP_001352711.1:p.Ala203Thr
LRG_387t1:c.715G>A
LRG_387:g.24950G>A
LRG_387p1:p.Ala239Thr
NC_000015.9:g.63354787G>A
NM_001018005.1:c.715G>A
p.(Ala239Thr)
p.Ala239Thr

Protein change:

A203T

Links:

Leiden Muscular Dystrophy (TPM1): TPM1_00026; dbSNP: rs199476318

NCBI 1000 Genomes Browser:

rs199476318

Molecular consequence:

NM_000366.6:c.715G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018004.2:c.715G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018005.2:c.715G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018006.2:c.715G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018007.2:c.715G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018008.2:c.607G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018020.2:c.715G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001301244.2:c.715G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001301289.2:c.607G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330344.2:c.607G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330346.2:c.607G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330351.2:c.607G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365776.1:c.715G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365777.1:c.715G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365778.1:c.841G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365779.1:c.715G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365780.1:c.607G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365781.2:c.607G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365782.1:c.607G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

probably has functional consequence

Condition(s)

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000547691	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 16, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20215591, 27532257, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000547691

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 16, 2018)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000547691.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces alanine with threonine at codon 239 of the TPM1 protein (p.Ala239Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (rs199476318, ExAC no frequency). This variant has been reported in individuals affected with dilated cardiomyopathy (PMID: 20215591, Invitae) and hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 31895). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Missense variants that are absent from the ExAC population database have been shown to be significantly overrepresented in individuals with hypertrophic and dilated cardiomyopathy (PMID: 27532257).

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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine