NM_001370466.1(NOD2):c.1065C>G (p.Asp355Glu) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 28, 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:: RCV003764528.2

Allele description [Variation Report for NM_001370466.1(NOD2):c.1065C>G (p.Asp355Glu)]

NM_001370466.1(NOD2):c.1065C>G (p.Asp355Glu)

Gene:

NOD2:nucleotide binding oligomerization domain containing 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q12.1

Genomic location:

Preferred name:

NM_001370466.1(NOD2):c.1065C>G (p.Asp355Glu)

HGVS:

NC_000016.10:g.50711057C>G
NG_007508.1:g.18919C>G
NM_001293557.2:c.1065C>G
NM_001370466.1:c.1065C>GMANE SELECT
NM_022162.3:c.1146C>G
NP_001280486.1:p.Asp355Glu
NP_001357395.1:p.Asp355Glu
NP_071445.1:p.Asp382Glu
LRG_177t1:c.1146C>G
LRG_177:g.18919C>G
LRG_177p1:p.Asp382Glu
NC_000016.9:g.50744968C>G
NM_022162.1:c.1146C>G
NR_163434.1:n.1130C>G
Q9HC29:p.Asp382Glu

Protein change:

D355E; ASP382GLU

Links:

UniProtKB: Q9HC29#VAR_023822; OMIM: 605956.0009; dbSNP: rs104895476

NCBI 1000 Genomes Browser:

rs104895476

Molecular consequence:

NM_001293557.2:c.1065C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370466.1:c.1065C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_022162.3:c.1146C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_163434.1:n.1130C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Blau syndrome (BLAUS)
Synonyms:: Synovitis granulomatous with uveitis and cranial neuropathies; Arthrocutaneouveal granulomatosis; Granulomatosis, familial, Blau type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008523; MedGen: C5201146; Orphanet: 90340; OMIM: 186580

Name:: Regional enteritis
Synonyms:: Enteritis, Granulomatous
Identifiers:: MeSH: D003424; MedGen: C0678202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004571000	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 28, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21596301, 24713464, 15459013, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004571000

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 28, 2023)

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

Uveitis in Blau syndrome from a de novo mutation of the NOD2/CARD15 gene.

Raiji VR, Miller MM, Jung LK.

J AAPOS. 2011 Apr;15(2):205-7. doi: 10.1016/j.jaapos.2011.02.004.

PubMed [citation]

PMID:: 21596301

Ultrasonographic assessment reveals detailed distribution of synovial inflammation in Blau syndrome.

Ikeda K, Kambe N, Takei S, Nakano T, Inoue Y, Tomiita M, Oyake N, Satoh T, Yamatou T, Kubota T, Okafuji I, Kanazawa N, Nishikomori R, Shimojo N, Matsue H, Nakajima H.

Arthritis Res Ther. 2014 Apr 8;16(2):R89. doi: 10.1186/ar4533.

PubMed [citation]

PMID:: 24713464
PMCID:: PMC4060485

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004571000.1

#	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 glutamic acid, which is acidic and polar, at codon 382 of the NOD2 protein (p.Asp382Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Blau syndrome (PMID: 15459013, 21596301, 24713464). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 4699). 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 NOD2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects NOD2 function (PMID: 15459013). 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: Sep 29, 2024

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