NM_033629.6(TREX1):c.598G>A (p.Asp200Asn) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 14, 2022
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:: RCV002512754.5

Allele description [Variation Report for NM_033629.6(TREX1):c.598G>A (p.Asp200Asn)]

NM_033629.6(TREX1):c.598G>A (p.Asp200Asn)

Genes:

ATRIP:ATR interacting protein [Gene - OMIM - HGNC]
ATRIP-TREX1:ATRIP-TREX1 readthrough [Gene]
TREX1:three prime repair exonuclease 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_033629.6(TREX1):c.598G>A (p.Asp200Asn)

HGVS:

NC_000003.12:g.48467253G>A
NG_009820.2:g.6424G>A
NG_033100.1:g.38608C>T
NG_033100.2:g.42557C>T
NG_041782.1:g.25544G>A
NG_099340.1:g.314G>A
NM_001271022.2:c.*1699G>A
NM_001271023.2:c.*1699G>A
NM_007248.5:c.568G>A
NM_032166.4:c.*1699G>A
NM_033629.6:c.598G>AMANE SELECT
NM_130384.3:c.*1699G>AMANE SELECT
NP_009179.2:p.Asp190Asn
NP_338599.1:p.Asp200Asn
NP_338599.1:p.Asp200Asn
LRG_282t1:c.598G>A
AAK07616.1:p.Asp200Asn
LRG_282:g.6424G>A
LRG_282p1:p.Asp200Asn
NC_000003.11:g.48508652G>A
NM_033629.4:c.598G>A
NR_153405.1:n.3907G>A
Q9NSU2:p.Asp255Asn

Protein change:

D190N; ASP200ASN

Links:

UniProtKB: Q9NSU2#VAR_032940; OMIM: 606609.0006; dbSNP: rs78846775

Molecular consequence:

NM_001271022.2:c.*1699G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001271023.2:c.*1699G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_032166.4:c.*1699G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_130384.3:c.*1699G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_007248.5:c.568G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033629.6:c.598G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_153405.1:n.3907G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Aicardi-Goutieres syndrome 1
Synonyms:: CREE ENCEPHALITIS; ENCEPHALOPATHY, FAMILIAL INFANTILE, WITH INTRACRANIAL CALCIFICATION AND CHRONIC CEREBROSPINAL FLUID LYMPHOCYTOSIS; PSEUDOTOXOPLASMOSIS SYNDROME
Identifiers:: MONDO: MONDO:0009165; MedGen: C0796126; Orphanet: 51; OMIM: 225750

Name:: Chilblain lupus 1 (CHBL1)
Identifiers:: MONDO: MONDO:0012500; MedGen: C0024145; OMIM: 610448

Name:: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS)
Synonyms:: CEREBRORETINAL VASCULOPATHY, HEREDITARY; RETINOPATHY, VASCULAR, WITH CEREBRAL AND RENAL INVOLVEMENT AND RAYNAUD AND MIGRAINE PHENOMENA
Identifiers:: MONDO: MONDO:0008641; MedGen: C1860518; Orphanet: 3421; Orphanet: 63261; Orphanet: 71291; OMIM: 192315

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003525218	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 14, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17357087, 20131292, 18805785, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003525218

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 14, 2022)

germline

clinical testing

PubMed (4)
[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

Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome.

Rice G, Newman WG, Dean J, Patrick T, Parmar R, Flintoff K, Robins P, Harvey S, Hollis T, O'Hara A, Herrick AL, Bowden AP, Perrino FW, Lindahl T, Barnes DE, Crow YJ.

Am J Hum Genet. 2007 Apr;80(4):811-5. Epub 2007 Feb 19.

PubMed [citation]

PMID:: 17357087
PMCID:: PMC1852703

Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutières syndrome.

Ramantani G, Kohlhase J, Hertzberg C, Innes AM, Engel K, Hunger S, Borozdin W, Mah JK, Ungerath K, Walkenhorst H, Richardt HH, Buckard J, Bevot A, Siegel C, von Stülpnagel C, Ikonomidou C, Thomas K, Proud V, Niemann F, Wieczorek D, Häusler M, Niggemann P, et al.

Arthritis Rheum. 2010 May;62(5):1469-77. doi: 10.1002/art.27367.

PubMed [citation]

PMID:: 20131292

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003525218.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 200 of the TREX1 protein (p.Asp200Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Aicardi-Goutieres syndrome (PMID: 17357087, 20131292). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 4184). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects TREX1 function (PMID: 18805785). 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

Last Updated: Jul 6, 2026

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