NM_001018005.2(TPM1):c.829G>A (p.Ala277Thr) AND Cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 28, 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:: RCV001192355.4

Allele description [Variation Report for NM_001018005.2(TPM1):c.829G>A (p.Ala277Thr)]

NM_001018005.2(TPM1):c.829G>A (p.Ala277Thr)

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.829G>A (p.Ala277Thr)

HGVS:

NC_000015.10:g.63064120G>A
NG_007557.1:g.26482G>A
NM_000366.6:c.829G>A
NM_001018004.2:c.772+1475G>A
NM_001018005.2:c.829G>AMANE SELECT
NM_001018006.2:c.772+1475G>A
NM_001018007.2:c.772+1475G>A
NM_001018008.2:c.664+1475G>A
NM_001018020.2:c.772+1475G>A
NM_001301244.2:c.829G>A
NM_001301289.2:c.664+1475G>A
NM_001330344.2:c.664+1475G>A
NM_001330346.2:c.721G>A
NM_001330351.2:c.664+1475G>A
NM_001365776.1:c.772+1475G>A
NM_001365777.1:c.772+1475G>A
NM_001365778.1:c.898+1475G>A
NM_001365779.1:c.829G>A
NM_001365780.1:c.664+1475G>A
NM_001365781.2:c.721G>A
NM_001365782.1:c.721G>A
NP_000357.3:p.Ala277Thr
NP_001018005.1:p.Ala277Thr
NP_001288173.1:p.Ala277Thr
NP_001317275.1:p.Ala241Thr
NP_001352708.1:p.Ala277Thr
NP_001352710.1:p.Ala241Thr
NP_001352711.1:p.Ala241Thr
LRG_387t1:c.829G>A
LRG_387:g.26482G>A
LRG_387p1:p.Ala277Thr
NC_000015.9:g.63356319G>A
NM_000366.5:c.829G>A
NM_001018005.1:c.829G>A
c.829G>A

Protein change:

A241T

Links:

dbSNP: rs149659674

NCBI 1000 Genomes Browser:

rs149659674

Molecular consequence:

NM_001018004.2:c.772+1475G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001018006.2:c.772+1475G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001018007.2:c.772+1475G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001018008.2:c.664+1475G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001018020.2:c.772+1475G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001301289.2:c.664+1475G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001330344.2:c.664+1475G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001330351.2:c.664+1475G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001365776.1:c.772+1475G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001365777.1:c.772+1475G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001365778.1:c.898+1475G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001365780.1:c.664+1475G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000366.6:c.829G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018005.2:c.829G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001301244.2:c.829G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330346.2:c.721G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365779.1:c.829G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365781.2:c.721G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365782.1:c.721G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001360403	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 28, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27532257, 32880476, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001360403

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 28, 2023)

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

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

Implications of Genetic Testing in Dilated Cardiomyopathy.

Verdonschot JAJ, Hazebroek MR, Krapels IPC, Henkens MTHM, Raafs A, Wang P, Merken JJ, Claes GRF, Vanhoutte EK, van den Wijngaard A, Heymans SRB, Brunner HG.

Circ Genom Precis Med. 2020 Oct;13(5):476-487. doi: 10.1161/CIRCGEN.120.003031. Epub 2020 Sep 3.

PubMed [citation]

PMID:: 32880476

See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001360403.3

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

Description

This missense variant replaces alanine with threonine at codon 277 of the TPM1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 27532257) and dilated cardiomyopathy (PMID: 32880476). This variant has been identified in 8/282436 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	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

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