NM_001018005.2(TPM1):c.850A>G (p.Ile284Val) AND not provided

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Nov 25, 2024
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:: RCV000024594.9

Allele description [Variation Report for NM_001018005.2(TPM1):c.850A>G (p.Ile284Val)]

NM_001018005.2(TPM1):c.850A>G (p.Ile284Val)

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.850A>G (p.Ile284Val)

Other names:

p.I284V:ATA>GTA

HGVS:

NC_000015.10:g.63064141A>G
NG_007557.1:g.26503A>G
NM_000366.6:c.850A>G
NM_001018004.2:c.772+1496A>G
NM_001018005.2:c.850A>GMANE SELECT
NM_001018006.2:c.772+1496A>G
NM_001018007.2:c.772+1496A>G
NM_001018008.2:c.664+1496A>G
NM_001018020.2:c.772+1496A>G
NM_001301244.2:c.850A>G
NM_001301289.2:c.664+1496A>G
NM_001330344.2:c.664+1496A>G
NM_001330346.2:c.742A>G
NM_001330351.2:c.664+1496A>G
NM_001365776.1:c.772+1496A>G
NM_001365777.1:c.772+1496A>G
NM_001365778.1:c.898+1496A>G
NM_001365779.1:c.850A>G
NM_001365780.1:c.664+1496A>G
NM_001365781.2:c.742A>G
NM_001365782.1:c.742A>G
NP_000357.3:p.Met284Val
NP_001018005.1:p.Ile284Val
NP_001288173.1:p.Ile284Val
NP_001317275.1:p.Ile248Val
NP_001352708.1:p.Met284Val
NP_001352710.1:p.Met248Val
NP_001352711.1:p.Met248Val
LRG_387t1:c.850A>G
LRG_387:g.26503A>G
LRG_387p1:p.Ile284Val
NC_000015.9:g.63356340A>G
NM_000366.5:c.850A>G
NM_001018005.1:c.850A>G
NM_001301244.1:c.850A>G
p.(Ile284Val)
r.(spl?)

Protein change:

I248V

Links:

Leiden Muscular Dystrophy (TPM1): TPM1_00029; dbSNP: rs199476322

NCBI 1000 Genomes Browser:

rs199476322

Molecular consequence:

NM_001018004.2:c.772+1496A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001018006.2:c.772+1496A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001018007.2:c.772+1496A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001018008.2:c.664+1496A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001018020.2:c.772+1496A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001301289.2:c.664+1496A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001330344.2:c.664+1496A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001330351.2:c.664+1496A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001365776.1:c.772+1496A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001365777.1:c.772+1496A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001365778.1:c.898+1496A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001365780.1:c.664+1496A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000366.6:c.850A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001018005.2:c.850A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001301244.2:c.850A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330346.2:c.742A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001365779.1:c.850A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001365781.2:c.742A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001365782.1:c.742A>G - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

functional variant [Sequence Ontology: SO:0001536]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000045903	Leiden Muscular Dystrophy (TPM1)	no classification provided	not provided	germline	curation	PubMed (1) [See all records that cite this PMID]
SCV000209337	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Nov 25, 2024)	germline	clinical testing	Citation Link,
SCV001924598	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV001972351	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing

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Summary from all submissions

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

Citations

PubMed

Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy.

Olivotto I, Girolami F, Ackerman MJ, Nistri S, Bos JM, Zachara E, Ommen SR, Theis JL, Vaubel RA, Re F, Armentano C, Poggesi C, Torricelli F, Cecchi F.

Mayo Clin Proc. 2008 Jun;83(6):630-8. doi: 10.4065/83.6.630.

PubMed [citation]

PMID:: 18533079

Details of each submission

From Leiden Muscular Dystrophy (TPM1), SCV000045903.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

#	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		not provided	not provided	not provided	not provided

From GeneDx, SCV000209337.14

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Reported in multiple individuals with HCM, sometimes referred to as M284V due to alternate nomenclature (PMID: 25031304, 18533079, 20159828, 23674513, 27532257, 30847666); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Functional studies demonstrated this variant did not perform significantly different compared to wildtype (PMID: 30240712); In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 30847666, 34681814, 27532257, 20159828, 33129908, Syomin2020, 18533079, 23674513, 29447731, 34137518, 25031304, 30240712, 37652022)

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

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001924598.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001972351.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

Last Updated: Feb 25, 2025

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