NM_001370466.1(NOD2):c.1196G>A (p.Arg399His) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 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:: RCV002528895.9

Allele description

NM_001370466.1(NOD2):c.1196G>A (p.Arg399His)

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.1196G>A (p.Arg399His)

HGVS:

NC_000016.10:g.50711188G>A
NG_007508.1:g.19050G>A
NM_001293557.2:c.1196G>A
NM_001370466.1:c.1196G>AMANE SELECT
NM_022162.1:c.1277G>A
NM_022162.3:c.1277G>A
NP_001280486.1:p.Arg399His
NP_001357395.1:p.Arg399His
NP_071445.1:p.Arg426His
LRG_177t1:c.1277G>A
LRG_177:g.19050G>A
NC_000016.9:g.50745099G>A
NM_022162.2:c.1277G>A
NR_163434.1:n.1261G>A

Protein change:

R399H

Links:

dbSNP: rs562225614

NCBI 1000 Genomes Browser:

rs562225614

Molecular consequence:

NM_001293557.2:c.1196G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370466.1:c.1196G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022162.3:c.1277G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_163434.1:n.1261G>A - 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
SCV000759525	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 28, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29697845, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000759525

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 28, 2023)

germline

clinical testing

PubMed (2)
[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

Novel NOD2 Mutation in Early-Onset Inflammatory Bowel Phenotype.

Girardelli M, Loganes C, Pin A, Stacul E, Decleva E, Vozzi D, Baj G, De Giacomo C, Tommasini A, Bianco AM.

Inflamm Bowel Dis. 2018 May 18;24(6):1204-1212. doi: 10.1093/ibd/izy061.

PubMed [citation]

PMID:: 29697845

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000759525.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 426 of the NOD2 protein (p.Arg426His). This variant is present in population databases (rs562225614, gnomAD 0.02%). This missense change has been observed in individual(s) with early-onset inflammatory bowel disease (PMID: 29697845). ClinVar contains an entry for this variant (Variation ID: 531600). Experimental studies have shown that this missense change affects NOD2 function (PMID: 29697845). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 16, 2024

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