NM_000359.3(TGM1):c.1121A>G (p.Tyr374Cys) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 6, 2023
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:: RCV001885294.6

Allele description [Variation Report for NM_000359.3(TGM1):c.1121A>G (p.Tyr374Cys)]

NM_000359.3(TGM1):c.1121A>G (p.Tyr374Cys)

Gene:

TGM1:transglutaminase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q12

Genomic location:

Preferred name:

NM_000359.3(TGM1):c.1121A>G (p.Tyr374Cys)

HGVS:

NC_000014.9:g.24259113T>C
NG_007150.2:g.9054A>G
NM_000359.3:c.1121A>GMANE SELECT
NP_000350.1:p.Tyr374Cys
NC_000014.8:g.24728319T>C
NG_007150.1:g.9054A>G

Protein change:

Y374C

Links:

dbSNP: rs2040782954

NCBI 1000 Genomes Browser:

rs2040782954

Molecular consequence:

NM_000359.3:c.1121A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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PREDICTED: Mus pahari cholinergic receptor nicotinic epsilon subunit (Chrne), mR...
PREDICTED: Mus pahari cholinergic receptor nicotinic epsilon subunit (Chrne), mRNA
gi|1195512681|ref|XM_021213457.1|

Nucleotide
Mus musculus regulator of G-protein signaling 6 (Rgs6), transcript variant 1, mR...
Mus musculus regulator of G-protein signaling 6 (Rgs6), transcript variant 1, mRNA
gi|2325513898|ref|NM_015812.5|

Nucleotide
LOC127888310 [Homo sapiens]
LOC127888310 [Homo sapiens]
Gene ID:127888310

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002292302	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 6, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27025581, 28403434, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002292302

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 6, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum of Autosomal Recessive Congenital Ichthyosis in Scandinavia: Clinical Characteristics and Novel and Recurrent Mutations in 132 Patients.

Pigg MH, Bygum A, Gånemo A, Virtanen M, Brandrup F, Zimmer AD, Hotz A, Vahlquist A, Fischer J.

Acta Derm Venereol. 2016 Nov 2;96(7):932-937. doi: 10.2340/00015555-2418.

PubMed [citation]

PMID:: 27025581

Expanding the Genotypic Spectrum of Bathing Suit Ichthyosis.

Marukian NV, Hu RH, Craiglow BG, Milstone LM, Zhou J, Theos A, Kaymakcalan H, Akkaya DA, Uitto JJ, Vahidnezhad H, Youssefian L, Bayliss SJ, Paller AS, Boyden LM, Choate KA.

JAMA Dermatol. 2017 Jun 1;153(6):537-543. doi: 10.1001/jamadermatol.2017.0202.

PubMed [citation]

PMID:: 28403434
PMCID:: PMC5817618

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002292302.3

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 1334159). This missense change has been observed in individuals with TGM1-related conditions (PMID: 27025581, 28403434). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 374 of the TGM1 protein (p.Tyr374Cys). This variant is not present in population databases (gnomAD no frequency).

#	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: Sep 29, 2024

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