NM_001018005.2(TPM1):c.253G>A (p.Val85Ile) AND Cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 9, 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:: RCV001526292.3

Allele description [Variation Report for NM_001018005.2(TPM1):c.253G>A (p.Val85Ile)]

NM_001018005.2(TPM1):c.253G>A (p.Val85Ile)

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.253G>A (p.Val85Ile)

HGVS:

NC_000015.10:g.63056997G>A
NG_007557.1:g.19359G>A
NM_000366.6:c.253G>A
NM_001018004.2:c.253G>A
NM_001018005.2:c.253G>AMANE SELECT
NM_001018006.2:c.253G>A
NM_001018007.2:c.253G>A
NM_001018008.2:c.145G>A
NM_001018020.2:c.253G>A
NM_001301244.2:c.253G>A
NM_001301289.2:c.145G>A
NM_001330344.2:c.145G>A
NM_001330346.2:c.145G>A
NM_001330351.2:c.145G>A
NM_001365776.1:c.253G>A
NM_001365777.1:c.253G>A
NM_001365778.1:c.379G>A
NM_001365779.1:c.253G>A
NM_001365780.1:c.145G>A
NM_001365781.2:c.145G>A
NM_001365782.1:c.145G>A
NP_000357.3:p.Val85Ile
NP_001018004.1:p.Val85Ile
NP_001018005.1:p.Val85Ile
NP_001018006.1:p.Val85Ile
NP_001018007.1:p.Val85Ile
NP_001018008.1:p.Val49Ile
NP_001018020.1:p.Val85Ile
NP_001288173.1:p.Val85Ile
NP_001288218.1:p.Val49Ile
NP_001317273.1:p.Val49Ile
NP_001317275.1:p.Val49Ile
NP_001317280.1:p.Val49Ile
NP_001352705.1:p.Val85Ile
NP_001352706.1:p.Val85Ile
NP_001352707.1:p.Val127Ile
NP_001352708.1:p.Val85Ile
NP_001352709.1:p.Val49Ile
NP_001352710.1:p.Val49Ile
NP_001352711.1:p.Val49Ile
LRG_387t1:c.253G>A
LRG_387:g.19359G>A
LRG_387p1:p.Val85Ile
NC_000015.9:g.63349196G>A
NM_001018005.1:c.253G>A

Protein change:

V127I

Links:

dbSNP: rs730881156

NCBI 1000 Genomes Browser:

rs730881156

Molecular consequence:

NM_000366.6:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018004.2:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018005.2:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018006.2:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018007.2:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018008.2:c.145G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018020.2:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001301244.2:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001301289.2:c.145G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330344.2:c.145G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330346.2:c.145G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330351.2:c.145G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365776.1:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365777.1:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365778.1:c.379G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365779.1:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365780.1:c.145G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365781.2:c.145G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365782.1:c.145G>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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RecName: Full=Gap junction alpha-1 protein; AltName: Full=Connexin-43; Short=Cx4...
RecName: Full=Gap junction alpha-1 protein; AltName: Full=Connexin-43; Short=Cx43; AltName: Full=Gap junction 43 kDa heart protein
gi|117708|sp|P08050.2|CXA1_RAT

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001736605	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 9, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29121657, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001736605

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 9, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hypertrophic cardiomyopathy clinical phenotype is independent of gene mutation and mutation dosage.

Viswanathan SK, Sanders HK, McNamara JW, Jagadeesan A, Jahangir A, Tajik AJ, Sadayappan S.

PLoS One. 2017;12(11):e0187948. doi: 10.1371/journal.pone.0187948.

PubMed [citation]

PMID:: 29121657
PMCID:: PMC5679632

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001736605.2

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

Description

This missense variant replaces valine with isoleucine at codon 85 of the TPM1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a familial case of hypertrophic cardiomyopathy with two carriers (PMID: 29121657). This variant has not been identified 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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