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NM_001243133.2(NLRP3):c.1699G>A (p.Glu567Lys) AND Cryopyrin associated periodic syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 24, 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:
RCV001224375.7

Allele description

NM_001243133.2(NLRP3):c.1699G>A (p.Glu567Lys)

Gene:
NLRP3:NLR family pyrin domain containing 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q44
Genomic location:
Preferred name:
NM_001243133.2(NLRP3):c.1699G>A (p.Glu567Lys)
HGVS:
  • NC_000001.11:g.247425148G>A
  • NG_007509.2:g.13976G>A
  • NM_001079821.3:c.1699G>A
  • NM_001127461.3:c.1699G>A
  • NM_001127462.3:c.1699G>A
  • NM_001243133.2:c.1699G>AMANE SELECT
  • NM_004895.5:c.1705G>A
  • NM_183395.3:c.1699G>A
  • NP_001073289.2:p.Glu567Lys
  • NP_001120933.2:p.Glu567Lys
  • NP_001120934.2:p.Glu567Lys
  • NP_001230062.1:p.Glu567Lys
  • NP_001230062.1:p.Glu567Lys
  • NP_004886.3:p.Glu569Lys
  • NP_004886.3:p.Glu569Lys
  • NP_899632.2:p.Glu567Lys
  • LRG_197t1:c.1705G>A
  • LRG_197:g.13976G>A
  • LRG_197p1:p.Glu569Lys
  • NC_000001.10:g.247588450G>A
  • NM_001243133.1:c.1699G>A
  • NM_004895.4:c.1705G>A
Protein change:
E567K
Links:
dbSNP: rs104895389
NCBI 1000 Genomes Browser:
rs104895389
Molecular consequence:
  • NM_001079821.3:c.1699G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127461.3:c.1699G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127462.3:c.1699G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243133.2:c.1699G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004895.5:c.1705G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_183395.3:c.1699G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cryopyrin associated periodic syndrome (CAPS)
Identifiers:
MONDO: MONDO:0016168; MedGen: C2316212

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001396565Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 24, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients.

Saito M, Nishikomori R, Kambe N, Fujisawa A, Tanizaki H, Takeichi K, Imagawa T, Iehara T, Takada H, Matsubayashi T, Tanaka H, Kawashima H, Kawakami K, Kagami S, Okafuji I, Yoshioka T, Adachi S, Heike T, Miyachi Y, Nakahata T.

Blood. 2008 Feb 15;111(4):2132-41. Epub 2007 Dec 6.

PubMed [citation]
PMID:
18063752

High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome: results of an International Multicenter Collaborative Study.

Tanaka N, Izawa K, Saito MK, Sakuma M, Oshima K, Ohara O, Nishikomori R, Morimoto T, Kambe N, Goldbach-Mansky R, Aksentijevich I, de Saint Basile G, Neven B, van Gijn M, Frenkel J, Aróstegui JI, Yagüe J, Merino R, Ibañez M, Pontillo A, Takada H, Imagawa T, et al.

Arthritis Rheum. 2011 Nov;63(11):3625-32. doi: 10.1002/art.30512.

PubMed [citation]
PMID:
21702021
PMCID:
PMC3498501
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001396565.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects NLRP3 function (PMID: 18063752, 21702021). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NLRP3 protein function. ClinVar contains an entry for this variant (Variation ID: 97944). This variant is also known as p.Glu567Lys, E567K, and 1699G>A. This missense change has been observed in individual(s) with cryopyrin-associated periodic syndromes (PMID: 18063752, 21702021, 25584041, 29163488). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 569 of the NLRP3 protein (p.Glu569Lys).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2024