NM_152263.4(TPM3):c.94C>T (p.Gln32Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 6, 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:: RCV003764563.1

Allele description [Variation Report for NM_152263.4(TPM3):c.94C>T (p.Gln32Ter)]

NM_152263.4(TPM3):c.94C>T (p.Gln32Ter)

Gene:

TPM3:tropomyosin 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.3

Genomic location:

Preferred name:

NM_152263.4(TPM3):c.94C>T (p.Gln32Ter)

HGVS:

NC_000001.11:g.154191925G>A
NG_008621.1:g.5209C>T
NM_001364679.2:c.94C>T
NM_001364680.2:c.94C>T
NM_001364681.2:c.94C>T
NM_001364682.1:c.94C>T
NM_152263.4:c.94C>TMANE SELECT
NP_001351608.1:p.Gln32Ter
NP_001351609.1:p.Gln32Ter
NP_001351610.1:p.Gln32Ter
NP_001351611.1:p.Gln32Ter
NP_689476.2:p.Gln32Ter
NP_689476.2:p.Gln32Ter
LRG_681t2:c.94C>T
LRG_681:g.5209C>T
LRG_681p2:p.Gln32Ter
NC_000001.10:g.154164401G>A
NM_152263.2:c.94C>T
NR_103460.2:n.176C>T
p.(Gln32*)

Protein change:

Q32*; GLN32TER

Links:

OMIM: 191030.0004; dbSNP: rs80358248

NCBI 1000 Genomes Browser:

rs80358248

Molecular consequence:

NR_103460.2:n.176C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001364679.2:c.94C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001364680.2:c.94C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001364681.2:c.94C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001364682.1:c.94C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_152263.4:c.94C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Congenital myopathy 4B, autosomal recessive
Synonyms:: Nemaline myopathy caused by mutation in the tropomyosin 3 gene; Nemaline myopathy 1, autosomal dominant or recessive
Identifiers:: MONDO: MONDO:0012239; MedGen: C5829889; Orphanet: 171433; Orphanet: 171439; Orphanet: 171881; OMIM: 609284

Name:: Congenital myopathy with fiber type disproportion
Synonyms:: Congenital fiber-type disproportion myopathy; Congenital Fiber-Type Disproportion
Identifiers:: MONDO: MONDO:0009711; MedGen: C0546264; Orphanet: 2020

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004569170	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 6, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27858751, 10619715, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004569170

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 6, 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

A Large Deletion Affecting TPM3, Causing Severe Nemaline Myopathy.

Kiiski K, Lehtokari VL, Manzur AY, Sewry C, Zaharieva I, Muntoni F, Pelin K, Wallgren-Pettersson C.

J Neuromuscul Dis. 2015 Sep 21;2(4):433-438.

PubMed [citation]

PMID:: 27858751
PMCID:: PMC5240603

Homozygosity for a nonsense mutation in the alpha-tropomyosin slow gene TPM3 in a patient with severe infantile nemaline myopathy.

Tan P, Briner J, Boltshauser E, Davis MR, Wilton SD, North K, Wallgren-Pettersson C, Laing NG.

Neuromuscul Disord. 1999 Dec;9(8):573-9.

PubMed [citation]

PMID:: 10619715

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004569170.1

#	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 creates a premature translational stop signal (p.Gln32*) in the TPM3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TPM3 are known to be pathogenic (PMID: 10619715, 27858751). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive congenital myopathy (PMID: 10619715). This variant is also known as a nonsense mutation at codon 31 (CAG to TAG). ClinVar contains an entry for this variant (Variation ID: 12449). For these reasons, this variant has been classified as Pathogenic.

#	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: Jul 15, 2024

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