NM_021942.6(TRAPPC11):c.1192C>T (p.Arg398Ter) AND Limb-girdle muscular dystrophy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 12, 2018
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:: RCV000825637.4

Allele description [Variation Report for NM_021942.6(TRAPPC11):c.1192C>T (p.Arg398Ter)]

NM_021942.6(TRAPPC11):c.1192C>T (p.Arg398Ter)

Gene:

TRAPPC11:trafficking protein particle complex subunit 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q35.1

Genomic location:

Preferred name:

NM_021942.6(TRAPPC11):c.1192C>T (p.Arg398Ter)

HGVS:

NC_000004.12:g.183682810C>T
NG_033102.1:g.28544C>T
NM_021942.6:c.1192C>TMANE SELECT
NM_199053.3:c.1192C>T
NP_068761.4:p.Arg398Ter
NP_951008.1:p.Arg398Ter
NP_951008.1:p.Arg398Ter
NC_000004.11:g.184603963C>T
NM_021942.5:c.1192C>T
NM_199053.2:c.1192C>T
p.Arg398X

Protein change:

R398*

Links:

dbSNP: rs140403642

NCBI 1000 Genomes Browser:

rs140403642

Molecular consequence:

NM_021942.6:c.1192C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_199053.3:c.1192C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Limb-girdle muscular dystrophy (LGMD)
Synonyms:: Muscular Dystrophies, Limb-Girdle
Identifiers:: MONDO: MONDO:0016971; MedGen: C0686353; Orphanet: 263; Human Phenotype Ontology: HP:0006785

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000967001	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Jul 12, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26322222, 27707803, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000967001

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Jul 12, 2018)

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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Congenital muscular dystrophy with fatty liver and infantile-onset cataract caused by TRAPPC11 mutations: broadening of the phenotype.

Liang WC, Zhu W, Mitsuhashi S, Noguchi S, Sacher M, Ogawa M, Shih HH, Jong YJ, Nishino I.

Skelet Muscle. 2015;5:29. doi: 10.1186/s13395-015-0056-4.

PubMed [citation]

PMID:: 26322222
PMCID:: PMC4551700

A novel TRAPPC11 mutation in two Turkish families associated with cerebral atrophy, global retardation, scoliosis, achalasia and alacrima.

Koehler K, Milev MP, Prematilake K, Reschke F, Kutzner S, Jühlen R, Landgraf D, Utine E, Hazan F, Diniz G, Schuelke M, Huebner A, Sacher M.

J Med Genet. 2017 Mar;54(3):176-185. doi: 10.1136/jmedgenet-2016-104108. Epub 2016 Oct 5.

PubMed [citation]

PMID:: 27707803

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967001.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

The p.Arg398X variant in TRAPPC11 has not been previously reported in literature but has been reported in ClinVar (Variation ID#474342). This variant has been i dentified in 0.004% (5/126674) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs140403642). Althoug h this variant has been seen in the general population, its frequency is low eno ugh to be consistent with a recessive carrier frequency. This nonsense variant l eads to a premature termination codon at position 398 which is predicted to lead to a truncated or absent protein. Biallelic variants in TRAPPC11 resulting in a truncated or absent protein have been reported in several patients with limb-gi rdle muscular dystrophy type 2S (Liang 2015, Koehler 2017). In summary, although additional studies are required to fully establish its clinical significance, t he p.Arg398X variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PVS1.

#	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		1	not provided	1	not provided

Last Updated: Sep 29, 2024

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