NM_001370466.1(NOD2):c.1234C>T (p.Arg412Cys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 13, 2024
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:: RCV002592534.10

Allele description [Variation Report for NM_001370466.1(NOD2):c.1234C>T (p.Arg412Cys)]

NM_001370466.1(NOD2):c.1234C>T (p.Arg412Cys)

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.1234C>T (p.Arg412Cys)

HGVS:

NC_000016.10:g.50711226C>T
NG_007508.1:g.19088C>T
NM_001293557.2:c.1234C>T
NM_001370466.1:c.1234C>TMANE SELECT
NM_022162.3:c.1315C>T
NP_001280486.1:p.Arg412Cys
NP_001357395.1:p.Arg412Cys
NP_071445.1:p.Arg439Cys
LRG_177:g.19088C>T
NC_000016.9:g.50745137C>T
NR_163434.1:n.1299C>T

Protein change:

R412C

Links:

dbSNP: rs375201229

NCBI 1000 Genomes Browser:

rs375201229

Molecular consequence:

NM_001293557.2:c.1234C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370466.1:c.1234C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_022162.3:c.1315C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_163434.1:n.1299C>T - 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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V175_0103_1006-like protein, partial [Amanita sp. 'cahokiana']
V175_0103_1006-like protein, partial [Amanita sp. 'cahokiana']
gi|926463001|gb|ALD18547.1|

Protein
V175_0103_1006-like protein, partial [Amanita sp. 'T31']
V175_0103_1006-like protein, partial [Amanita sp. 'T31']
gi|926463003|gb|ALD18548.1|

Protein
Decanoic Acids
Decanoic Acids
10-carbon saturated monocarboxylic acids.<br/>Year introduced: 1975

MeSH
Prostanoic Acids
Prostanoic Acids
2-Octylcyclopentaneheptanoic acids. The family of saturated carbon-20 cyclic fatty acids that represent the parent compounds of the prostaglandins.<br/>Year introduced: 1991(1975)

MeSH
Ascariasis
Ascariasis
Infection by nematodes of the genus ASCARIS. Ingestion of infective eggs causes diarrhea and pneumonitis. Its distribution is more prevalent in areas of poor sanitation and wh...<br/>

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002269210	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 13, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002269210

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 13, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002269210.3

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

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 439 of the NOD2 protein (p.Arg439Cys). This variant is present in population databases (rs375201229, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NOD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1484179). 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 not expected to disrupt NOD2 protein function with a negative predictive value of 95%. 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: Nov 10, 2024

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