ClinVar Genomic variation as it relates to human health
NM_000359.3(TGM1):c.428G>A (p.Arg143His)
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.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000359.3(TGM1):c.428G>A (p.Arg143His)
Variation ID: 12481 Accession: VCV000012481.44
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 14q12 14: 24261775 (GRCh38) [ NCBI UCSC ] 14: 24730981 (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 Apr 4, 2013 Feb 14, 2024 Jul 15, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000359.3:c.428G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000350.1:p.Arg143His missense NC_000014.9:g.24261775C>T NC_000014.8:g.24730981C>T NG_007150.1:g.6392G>A P22735:p.Arg143His - Protein change
- R143H
- Other names
- R142H
- Canonical SPDI
- NC_000014.9:24261774:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe 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.
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
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 | ||
---|---|---|---|---|---|---|
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. |
|||
TGM1 | - | - |
GRCh38 GRCh38 GRCh37 |
977 | 1010 |
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. |
---|---|---|---|---|
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Jul 15, 2023 | RCV000013299.28 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jul 10, 2021 | RCV001836706.9 | |
Pathogenic (1) |
criteria provided, single submitter
|
Mar 3, 2023 | RCV001387567.12 |
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. |
More information
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
(Jan 10, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive congenital ichthyosis 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000788532.1
First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015 |
|
|
Pathogenic
(Jul 10, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Abnormality of the skin
Affected status: yes
Allele origin:
germline
|
Kariminejad - Najmabadi Pathology & Genetics Center
Accession: SCV000927073.2
First in ClinVar: Jul 24, 2019 Last updated: Feb 20, 2022 |
|
|
Likely pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive congenital ichthyosis 1
Affected status: unknown
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002763962.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
|
|
Pathogenic
(Jul 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive congenital ichthyosis 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004203782.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
Pathogenic
(Mar 03, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001588235.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 143 of the TGM1 protein (p.Arg143His). … (more)
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 143 of the TGM1 protein (p.Arg143His). This variant is present in population databases (rs121918719, gnomAD 0.004%). This missense change has been observed in individuals with autosomal recessive congenital ichthyosis (PMID: 27025581, 31168818). ClinVar contains an entry for this variant (Variation ID: 12481). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TGM1 protein function. Experimental studies have shown that this missense change affects TGM1 function (PMID: 9593710). This variant disrupts the p.Arg143 amino acid residue in TGM1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9326318, 26220141, 28403434). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Nov 01, 2006)
|
no assertion criteria provided
Method: literature only
|
ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 1, WITH OR WITHOUT BATHING SUIT DISTRIBUTION
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000033546.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In 2 affected cousins from a consanguineous Egyptian family with severe autosomal recessive congenital ichthyosis (ARCI1; 242300) of the lamellar form, Russell et al. (1995) … (more)
In 2 affected cousins from a consanguineous Egyptian family with severe autosomal recessive congenital ichthyosis (ARCI1; 242300) of the lamellar form, Russell et al. (1995) identified homozygosity for a 1492G-A transition in exon 3 of the TGM1 gene, resulting in an arg142-to-his (R142H) substitution at a highly conserved residue. The mutation was present in heterozygosity in the unaffected parents, but was not found in 102 Egyptian control alleles. In a 35-year-old Dutch woman with ARCI in a bathing suit distribution, Oji et al. (2006) identified compound heterozygosity for the R142H mutation and a 376C-T transition in exon 3 of the TGM1 gene, resulting in an arg126-to-cys (R126C; 190195.0030) substitution at a residue at the beginning of the beta-sandwich domain. Her unaffected parents were each heterozygous for one of the mutations, neither of which was found in 100 control chromosomes. In situ TGase testing of an unaffected area of the patient's skin demonstrated a marked decrease in enzyme activity when the temperature was increased from 25 to 37 degrees Celsius. Oji et al. (2006) concluded that the bathing suit distribution of ichthyosis represents a temperature-sensitive phenotype. (less)
|
|
Pathogenic
(Mar 03, 2021)
|
no assertion criteria provided
Method: clinical testing
|
Autosomal recessive congenital ichthyosis type 1
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002091235.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Genotype-phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis. | Simpson JK | The British journal of dermatology | 2020 | PMID: 31168818 |
Expanding the Genotypic Spectrum of Bathing Suit Ichthyosis. | Marukian NV | JAMA dermatology | 2017 | PMID: 28403434 |
Spectrum of Autosomal Recessive Congenital Ichthyosis in Scandinavia: Clinical Characteristics and Novel and Recurrent Mutations in 132 Patients. | Pigg MH | Acta dermato-venereologica | 2016 | PMID: 27025581 |
Long-term faithful recapitulation of transglutaminase 1-deficient lamellar ichthyosis in a skin-humanized mouse model, and insights from proteomic studies. | Aufenvenne K | The Journal of investigative dermatology | 2012 | PMID: 22437313 |
Transglutaminase-1 gene mutations in autosomal recessive congenital ichthyosis: summary of mutations (including 23 novel) and modeling of TGase-1. | Herman ML | Human mutation | 2009 | PMID: 19241467 |
Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for a temperature-sensitive phenotype. | Oji V | Human molecular genetics | 2006 | PMID: 16968736 |
Transglutaminase 1 mutations in lamellar ichthyosis. Loss of activity due to failure of activation by proteolytic processing. | Candi E | The Journal of biological chemistry | 1998 | PMID: 9593710 |
Transglutaminase 1 mutations in autosomal recessive congenital ichthyosis: private and recurrent mutations in an isolated population. | Laiho E | American journal of human genetics | 1997 | PMID: 9326318 |
Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis. | Russell LJ | Nature genetics | 1995 | PMID: 7773290 |
Text-mined citations for rs121918719 ...
HelpRecord last updated May 12, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.