ClinVar Miner

Submissions for variant NM_001243133.1(NLRP3):c.902G>A (p.Gly301Asp) (rs180177441)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002580 SCV001160553 likely pathogenic not specified 2019-05-18 criteria provided, single submitter clinical testing The NLRP3 c.908G>A; p.Gly303Asp variant (rs180177441), also published as c.902G>A; p.Gly301Asp on NM_001243133.1, is reported in the medical literature and a gene-specific database in at least two individuals with CAPS (see link below, Han 2019). The variant is listed in the ClinVar database (Variation ID: 97978) but is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The amino acid at this position is highly conserved and computational algorithms predict this variant is deleterious. Additionally, this amino acid is located in the extended Walker B motif in the NACHT domain, critical in ATP hydrolysis (MacDonald 2013). Considering available information, this variant is classified as likely pathogenic. References: Link to NLRP3-specific database: https://infevers.umai-montpellier.fr/web/search.php?n=4 Han et al. The First Case Series of Cryopyrin-Associated Periodic Syndrome in Korea. Allergy Asthma Immunol Res. 2019 May; 11(3):e37. MacDonald JA et al. Biochemical and structural aspects of the ATP-binding domain in inflammasome-forming human NLRP proteins. IUBMB Life. 2013 Oct;65(10):851-62. Van Gijn ME et al. New workflow for classification of genetic variants' pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID). J Med Genet. 2018 Aug;55(8):530-537.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000084239 SCV000116375 not provided Familial cold urticaria no assertion provided not provided

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