VCV000012451.4 - ClinVar

NM_152263.4(TPM3):c.855del (p.Ter286AsnextTer?)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Likely pathogenic
Likely pathogenic (1)

1 out of 3 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_152263.4(TPM3):c.855del (p.Ter286AsnextTer?)

Variation ID: 12451 Accession: VCV000012451.4

Type and length

Deletion, 1 bp

Location

Cytogenetic: 1q21.3 1: 154167940 (GRCh38) [ NCBI UCSC ] 1: 154140416 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 23, 2014	Jun 20, 2026	May 13, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_152263.4:c.855del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_689476.2:p.Ter286AsnextTer?	frameshift
NM_001043351.2:c.664+2460del		intron variant
NM_001043352.2:c.664+2460del		intron variant
NM_001043353.2:c.664+2460del		intron variant
NM_001278188.2:c.466+2460del		intron variant
NM_001278189.2:c.743+1365del		intron variant
NM_001278190.2:c.601+2460del		intron variant
NM_001278191.2:c.394+2460del		intron variant
NM_001349679.2:c.743+1365del		intron variant
NM_001364679.2:c.775+2460del		intron variant
NM_001364680.2:c.775+2460del		intron variant
NM_001364681.2:c.775+2460del		intron variant
NM_001364682.1:c.855del	NP_001351611.1:p.Ter286AsnextTer?	frameshift
NM_001364683.1:c.744del	NP_001351612.1:p.Ter249AsnextTer?	frameshift
NM_153649.4:c.664+2460del		intron variant
NC_000001.11:g.154167940del
NC_000001.10:g.154140416del
NG_008621.1:g.29194del
LRG_681:g.29194del
LRG_681t1:c.664+2460del
LRG_681t2:c.855del	LRG_681p2:p.Ter286AsnextTer?
LRG_681t3:c.664+2460del

... more HGVS ... less HGVS

Protein change

Other names

p.*286Asnext*74

Canonical SPDI

NC_000001.11:154167939:T:

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA232702 OMIM: 191030.0006 dbSNP: rs199474719 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
TPM3		-	-	GRCh38 GRCh37	436	460

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Congenital myopathy 4B, autosomal recessive	Likely pathogenic (2)	criteria provided, single submitter	May 13, 2025	RCV000013266.29
not provided	not provided (1)	no classification provided	-	RCV000128707.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (May 13, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Congenital myopathy 4B, autosomal recessive	3billion Accession: SCV007611351.1 First in ClinVar: Jun 20, 2026 Last updated: Jun 20, 2026	Publications: PubMed (1) PubMed: 18382475 Comment: show The variant is not observed in the gnomAD v4.1.0 dataset. Predicted Consequence/Location: Frameshift: predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10%. The variant has been observed in at least two similarly affected unrelated individuals (PMID: 18382475). The variant has been reported to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated families (PMID: 18382475). The variant has been reported to be associated with TPM3-related disorder (ClinVar ID: VCV000012451). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Platform type: genome sequencing

Pathogenic (Sep 01, 2008) N Not contributing to aggregate classification	no assertion criteria provided	CONGENITAL MYOPATHY 4B, AUTOSOMAL RECESSIVE	OMIM Accession: SCV000033513.5 First in ClinVar: Apr 04, 2013 Last updated: Jul 23, 2024	Publications: PubMed (1) PubMed: 18382475 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: In 4 patients from 2 presumably unrelated Turkish families with autosomal recessive congenital myopathy-4B (CMYO4B; 609284), Lehtokari et al. (2008) identified a homozygous 1-bp deletion … (more) In 4 patients from 2 presumably unrelated Turkish families with autosomal recessive congenital myopathy-4B (CMYO4B; 609284), Lehtokari et al. (2008) identified a homozygous 1-bp deletion (c.913delA, NM_152263) in exon 9b of the TPM3 gene, at the last nucleotide before the stop codon. The mutation was predicted to result in elongation of the protein by 73 residues, which would disrupt the coiled-coil polymer and render the protein nonfunctional. A shared haplotype between the 2 families suggested a founder effect. The phenotype was moderate to severe, with early-onset, restrictive respiratory vital capacity, and chest deformities. (less)

not provided (-) N Not contributing to aggregate classification	no classification provided	not provided	TPM3 homepage - Leiden Muscular Dystrophy pages Accession: SCV000172347.1 First in ClinVar: Jul 23, 2014 Last updated: Jul 23, 2014	Observation: 1 Collection method: not provided Allele origin: germline Affected status: not provided Observation 1 Collection method: not provided Allele origin: germline Affected status: not provided

Comment:

The variant is not observed in the gnomAD v4.1.0 dataset. Predicted Consequence/Location: Frameshift: predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10%. The variant has been observed in at least two similarly affected unrelated individuals (PMID: 18382475). The variant has been reported to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated families (PMID: 18382475). The variant has been reported to be associated with TPM3-related disorder (ClinVar ID: VCV000012451). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Identification of a founder mutation in TPM3 in nemaline myopathy patients of Turkish origin.	Lehtokari VL	European journal of human genetics : EJHG	2008	PMID: 18382475

Text-mined citations for rs199474719 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 27, 2026