NM_003289.4(TPM2):c.14AGA[2] (p.Lys7del) AND Arthrogryposis, distal, type 1A

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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 5, 2022
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:: RCV000795370.4

Allele description

NM_003289.4(TPM2):c.14AGA[2] (p.Lys7del)

Gene:

TPM2:tropomyosin 2 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

9p13.3

Genomic location:

Preferred name:

NM_003289.4(TPM2):c.14AGA[2] (p.Lys7del)

HGVS:

NC_000009.12:g.35689797CTT[2]
NG_011620.1:g.5254AGA[2]
NM_001301226.2:c.14AGA[2]
NM_001301227.2:c.14AGA[2]
NM_003289.4:c.14AGA[2]MANE SELECT
NM_213674.1:c.14AGA[2]
NP_001288155.1:p.Lys7del
NP_001288156.1:p.Lys7del
NP_003280.2:p.Lys7del
NP_998839.1:p.Lys7del
LRG_680t1:c.14AGA[2]
LRG_680:g.5254AGA[2]
LRG_680p1:p.Lys7del
NC_000009.11:g.35689793_35689795del
NC_000009.11:g.35689794CTT[2]
NM_003289.3:c.20_22delAGA
NM_003289.4:c.20_22delMANE SELECT
p.(Lys7del)

Protein change:

K7del

Links:

OMIM: 190990.0009; dbSNP: rs199476146

NCBI 1000 Genomes Browser:

rs199476146

Molecular consequence:

NM_001301226.2:c.14AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001301227.2:c.14AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_003289.4:c.14AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_213674.1:c.14AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Arthrogryposis, distal, type 1A
Synonyms:: ARTHROGRYPOSIS MULTIPLEX CONGENITA, DISTAL, TYPE I
Identifiers:: MONDO: MONDO:0007157; MedGen: C0220662; Orphanet: 1146; OMIM: 108120

Recent activity

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Neoregelia cruenta isolate B172 tRNA-Ser (trnS) gene, partial sequence; trns-trn...
Neoregelia cruenta isolate B172 tRNA-Ser (trnS) gene, partial sequence; trns-trnG intergenic spacer, complete sequence; photosystem II protein Z (psbZ) gene, complete cds; and tRNA-Gly (trnG) gene, partial sequence; chloroplast
gi|284192303|gb|FJ968371.1|

Nucleotide
Neoregelia cruenta tRNA-Lys (trnK) gene, partial sequence; and maturase K (matK)...
Neoregelia cruenta tRNA-Lys (trnK) gene, partial sequence; and maturase K (matK) gene, partial cds; chloroplast
gi|650271818|gb|KJ580089.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000934833	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 5, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 26307083, 22980765, 23378224, 23413262, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000934833

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 5, 2022)

germline

clinical testing

PubMed (5)
[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

Muscle weakness in TPM3-myopathy is due to reduced Ca2+-sensitivity and impaired acto-myosin cross-bridge cycling in slow fibres.

Yuen M, Cooper ST, Marston SB, Nowak KJ, McNamara E, Mokbel N, Ilkovski B, Ravenscroft G, Rendu J, de Winter JM, Klinge L, Beggs AH, North KN, Ottenheijm CA, Clarke NF.

Hum Mol Genet. 2015 Nov 15;24(22):6278-92. doi: 10.1093/hmg/ddv334. Epub 2015 Aug 24.

PubMed [citation]

PMID:: 26307083
PMCID:: PMC4614700

Whole-Body muscle MRI in a series of patients with congenital myopathy related to TPM2 gene mutations.

Jarraya M, Quijano-Roy S, Monnier N, Béhin A, Avila-Smirnov D, Romero NB, Allamand V, Richard P, Barois A, May A, Estournet B, Mercuri E, Carlier PG, Carlier RY.

Neuromuscul Disord. 2012 Oct 1;22 Suppl 2:S137-47. doi: 10.1016/j.nmd.2012.06.347.

PubMed [citation]

PMID:: 22980765

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000934833.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects TPM2 function (PMID: 23378224, 23413262, 26307083). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 140486). This variant is also known as c.19_21delAAG. This variant has been observed in individual(s) with autosomal dominant congenital myopathy (PMID: 22980765, 23378224, 23413262). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This variant, c.20_22del, results in the deletion of 1 amino acid(s) of the TPM2 protein (p.Lys7del), but otherwise preserves the integrity of the reading frame.

#	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 29, 2024

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