NM_000359.3(TGM1):c.160C>T (p.Arg54Ter) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Dec 16, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001579617.9

Allele description [Variation Report for NM_000359.3(TGM1):c.160C>T (p.Arg54Ter)]

NM_000359.3(TGM1):c.160C>T (p.Arg54Ter)

Gene:

TGM1:transglutaminase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q12

Genomic location:

Preferred name:

NM_000359.3(TGM1):c.160C>T (p.Arg54Ter)

HGVS:

NC_000014.9:g.24262193G>A
NG_007150.1:g.5974C>T
NM_000359.3:c.160C>TMANE SELECT
NP_000350.1:p.Arg54Ter
NC_000014.8:g.24731399G>A
NM_000359.2:c.160C>T

Protein change:

R54*

Links:

dbSNP: rs140000324

NCBI 1000 Genomes Browser:

rs140000324

Molecular consequence:

NM_000359.3:c.160C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001807906	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001959082	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV002239751	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 16, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 18948357, 19241467, 25766764, 27025581, 31168818, 28492532
SCV003924760	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 8, 2022)	germline	clinical testing	Citation Link

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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel transglutaminase-1 mutations and genotype-phenotype investigations of 104 patients with autosomal recessive congenital ichthyosis in the USA.

Farasat S, Wei MH, Herman M, Liewehr DJ, Steinberg SM, Bale SJ, Fleckman P, Toro JR.

J Med Genet. 2009 Feb;46(2):103-11. doi: 10.1136/jmg.2008.060905. Epub 2008 Oct 23.

PubMed [citation]

PMID:: 18948357
PMCID:: PMC3044481

Transglutaminase-1 gene mutations in autosomal recessive congenital ichthyosis: summary of mutations (including 23 novel) and modeling of TGase-1.

Herman ML, Farasat S, Steinbach PJ, Wei MH, Toure O, Fleckman P, Blake P, Bale SJ, Toro JR.

Hum Mutat. 2009 Apr;30(4):537-47. doi: 10.1002/humu.20952. Review.

PubMed [citation]

PMID:: 19241467
PMCID:: PMC3243309

See all PubMed Citations (6)

Details of each submission

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001807906.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001959082.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV002239751.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Arg54*) in the TGM1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TGM1 are known to be pathogenic (PMID: 18948357, 19241467). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with TGM1-related conditions (PMID: 19241467, 25766764, 27025581, 31168818). ClinVar contains an entry for this variant (Variation ID: 554786). 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

From GeneDx, SCV003924760.1

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

Description

Observed multiple times with a second variant in unrelated patients with lamellar ichthyosis or congenital ichthyosiform erythroderma in the published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes in all cases (Numata et al., 2015; Hellstrom Pigg et al., 2016; Simpson et al., 2020); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25766764, 23096117, 27025581, 19241467, 25281896, 31168818)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 6, 2024

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