NM_000359.3(TGM1):c.1186C>T (p.Arg396Cys) AND Autosomal recessive congenital ichthyosis 1

Germline classification:: Likely pathogenic (4 submissions)
Last evaluated:: Jun 8, 2018
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:: RCV000782372.7

Allele description [Variation Report for NM_000359.3(TGM1):c.1186C>T (p.Arg396Cys)]

NM_000359.3(TGM1):c.1186C>T (p.Arg396Cys)

Gene:

TGM1:transglutaminase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q12

Genomic location:

Preferred name:

NM_000359.3(TGM1):c.1186C>T (p.Arg396Cys)

HGVS:

NC_000014.9:g.24258647G>A
NG_007150.1:g.9520C>T
NM_000359.3:c.1186C>TMANE SELECT
NP_000350.1:p.Arg396Cys
NC_000014.8:g.24727853G>A
NM_000359.2:c.1186C>T
NM_000359.2:c.[1186C>T]

Protein change:

R396C

Links:

dbSNP: rs543521135

NCBI 1000 Genomes Browser:

rs543521135

Molecular consequence:

NM_000359.3:c.1186C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive congenital ichthyosis 1 (LI1)
Synonyms:: COLLODION FETUS; DESQUAMATION OF NEWBORN; ICHTHYOSIS CONGENITA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009441; MedGen: C4551630; OMIM: 242300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000920893	Uitto Lab, Thomas Jefferson University - Rare heritable connective tissue and skin disorders in Iranian cohort	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 8, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002072909	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002091221	Natera, Inc.	no assertion criteria provided	Pathogenic (Apr 27, 2021)	germline	clinical testing
SCV002763651	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Uitto Lab, Thomas Jefferson University - Rare heritable connective tissue and skin disorders in Iranian cohort, SCV000920893.1

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

#	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 Neuberg Centre For Genomic Medicine, NCGM, SCV002072909.1

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

Description

The missense variant p.R396C in TGM1 (NM_000359.3) has been previously submitted to ClinVar as Pathogenic, however no details are available for independent assessment. It has been reported in individuals with icthyosis (Nasser KK et al). Other missense mutations affecting the same amino acid have been reported previously (R396S, R396L). The p.R396C variant is observed in 2/30,616 (0.0065%) alleles from individuals of South Asian background in gnomAD Exomes and in 1/978 (0.1022%) alleles from individuals of South Asian background in 1000 Genomes. The p.R396C missense variant is predicted to be damaging by both SIFT and PolyPhen2.The arginine residue at codon 396 of TGM1 is conserved in all mammalian species. The nucleotide c.1186 in TGM1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.

#	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 Natera, Inc., SCV002091221.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002763651.1

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

#	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: Jan 13, 2025

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