NM_001370466.1(NOD2):c.1918G>A (p.Glu640Lys) AND multiple conditions

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 26, 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:: RCV002545422.9

Allele description

NM_001370466.1(NOD2):c.1918G>A (p.Glu640Lys)

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.1918G>A (p.Glu640Lys)

HGVS:

NC_000016.10:g.50711910G>A
NG_007508.1:g.19772G>A
NM_001293557.2:c.1918G>A
NM_001370466.1:c.1918G>AMANE SELECT
NM_022162.3:c.1999G>A
NP_001280486.1:p.Glu640Lys
NP_001357395.1:p.Glu640Lys
NP_071445.1:p.Glu667Lys
LRG_177:g.19772G>A
NC_000016.9:g.50745821G>A
NR_163434.1:n.1983G>A

Protein change:

E640K

Links:

dbSNP: rs774425599

NCBI 1000 Genomes Browser:

rs774425599

Molecular consequence:

NM_001293557.2:c.1918G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370466.1:c.1918G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022162.3:c.1999G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_163434.1:n.1983G>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
SCV002111391	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 26, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27625029, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002111391

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 26, 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

A Novel Mutation in Helical Domain 2 of NOD2 in Sporadic Blau Syndrome.

Jain L, Gupta N, Reddy MM, Mittal R, Barik MR, Panigrahi B, Monie T, Basu S.

Ocul Immunol Inflamm. 2018;26(2):292-294. doi: 10.1080/09273948.2016.1207789. Epub 2016 Sep 13.

PubMed [citation]

PMID:: 27625029
PMCID:: PMC5849224

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, SCV002111391.3

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

Description

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. ClinVar contains an entry for this variant (Variation ID: 1351101). This missense change has been observed in individual(s) with clinical features of Blau syndrome (PMID: 27625029). This variant is present in population databases (rs774425599, gnomAD 0.01%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 667 of the NOD2 protein (p.Glu667Lys). 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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