NM_001018005.2(TPM1):c.849del (p.Ile284fs) AND Hypertrophic cardiomyopathy

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 20, 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:: RCV004014121.1

Allele description

NM_001018005.2(TPM1):c.849del (p.Ile284fs)

Gene:

TPM1:tropomyosin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q22.2

Genomic location:

Preferred name:

NM_001018005.2(TPM1):c.849del (p.Ile284fs)

HGVS:

NC_000015.10:g.63064140del
NG_007557.1:g.26502del
NM_000366.6:c.849del
NM_001018004.2:c.772+1495del
NM_001018005.2:c.849delMANE SELECT
NM_001018006.2:c.772+1495del
NM_001018007.2:c.772+1495del
NM_001018008.2:c.664+1495del
NM_001018020.2:c.772+1495del
NM_001301244.2:c.849del
NM_001301289.2:c.664+1495del
NM_001330344.2:c.664+1495del
NM_001330346.2:c.741del
NM_001330351.2:c.664+1495del
NM_001365776.1:c.772+1495del
NM_001365777.1:c.772+1495del
NM_001365778.1:c.898+1495del
NM_001365779.1:c.849del
NM_001365780.1:c.664+1495del
NM_001365781.2:c.741del
NM_001365782.1:c.741del
NM_001407322.1:c.975del
NM_001407323.1:c.975del
NM_001407324.1:c.975del
NM_001407325.1:c.*1331del
NM_001407326.1:c.849del
NM_001407327.1:c.772+1495del
NM_001407328.1:c.772+1495del
NM_001407329.1:c.849del
NM_001407330.1:c.849del
NM_001407331.1:c.849del
NM_001407332.1:c.849del
NM_001407333.1:c.849del
NM_001407334.1:c.849del
NM_001407335.1:c.849del
NM_001407336.1:c.772+1495del
NM_001407337.1:c.772+1495del
NM_001407338.1:c.772+1495del
NM_001407340.1:c.*1331del
NM_001407341.1:c.*1331del
NM_001407342.1:c.664+1495del
NM_001407344.1:c.741del
NP_000357.3:p.Met284fs
NP_001018005.1:p.Ile284fs
NP_001288173.1:p.Ile284fs
NP_001317275.1:p.Ile248fs
NP_001352708.1:p.Met284fs
NP_001352710.1:p.Met248fs
NP_001352711.1:p.Met248fs
NP_001394251.1:p.Ile326fs
NP_001394252.1:p.Met326fs
NP_001394253.1:p.Met326fs
NP_001394255.1:p.Ser283_Ile284insTer
NP_001394258.1:p.Ile284fs
NP_001394259.1:p.Met284fs
NP_001394260.1:p.Ile284fs
NP_001394261.1:p.Met284fs
NP_001394262.1:p.Met284fs
NP_001394263.1:p.Met284fs
NP_001394264.1:p.Met284fs
NP_001394273.1:p.Ile248fs
LRG_387t1:c.849del
LRG_387:g.26502del
LRG_387p1:p.Ile284fs
NC_000015.9:g.63356339del
NR_176339.1:n.1103del
NR_176341.1:n.1008del
NR_176342.1:n.1008del
NR_176343.1:n.1008del
NR_176345.1:n.1008del
NR_176346.1:n.1008del
NR_176351.1:n.2322del

Protein change:

I248fs

Molecular consequence:

NM_001407325.1:c.*1331del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001407340.1:c.*1331del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001407341.1:c.*1331del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000366.6:c.849del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001018005.2:c.849del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001301244.2:c.849del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330346.2:c.741del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001365779.1:c.849del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001365781.2:c.741del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001365782.1:c.741del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407322.1:c.975del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407323.1:c.975del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407324.1:c.975del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407326.1:c.849del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407329.1:c.849del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407330.1:c.849del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407331.1:c.849del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407332.1:c.849del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407333.1:c.849del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407334.1:c.849del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407335.1:c.849del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407344.1:c.741del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001018004.2:c.772+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001018006.2:c.772+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001018007.2:c.772+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001018008.2:c.664+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001018020.2:c.772+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001301289.2:c.664+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001330344.2:c.664+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001330351.2:c.664+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001365776.1:c.772+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001365777.1:c.772+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001365778.1:c.898+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001365780.1:c.664+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407327.1:c.772+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407328.1:c.772+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407336.1:c.772+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407337.1:c.772+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407338.1:c.772+1495del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407342.1:c.664+1495del - intron variant - [Sequence Ontology: SO:0001627]
NR_176339.1:n.1103del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176341.1:n.1008del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176342.1:n.1008del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176343.1:n.1008del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176345.1:n.1008del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176346.1:n.1008del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176351.1:n.2322del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

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

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Gene ID:158471

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004838216	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Nov 20, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004838216

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Nov 20, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

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 All of Us Research Program, National Institutes of Health, SCV004838216.1

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

Description

This variant deletes 1 nucleotide in exon 9 of the TPM1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with TPM1-related disorders in the literature. This variant has been identified in 1/250560 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Clinical relevance of loss-of-function TPM1 truncation variants in autosomal dominant cardiovascular disorders is not clearly established. 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	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 1, 2024

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