Submissions for variant NM_001243133.2(NLRP3):c.1389C>T (p.His463=)

gnomAD frequency: 0.00354  dbSNP: rs111400208

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000084190	SCV000356961	benign	Familial cold autoinflammatory syndrome 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000401266	SCV000356962	benign	Chronic infantile neurological, cutaneous and articular syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000303340	SCV000356963	benign	Familial amyloid nephropathy with urticaria AND deafness	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000755589	SCV000604558	benign	not provided	2023-10-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082261	SCV000646262	benign	Cryopyrin associated periodic syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000249054	SCV000967099	benign	not specified	2017-08-23	criteria provided, single submitter	clinical testing	p.His465His in exon 5 of NLRP3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 0.64% (42/6592) of F innish chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadi nstitute.org; dbSNP rs111400208).
Athena Diagnostics	RCV000755589	SCV001144768	benign	not provided	2019-02-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000755589	SCV001891299	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262692	SCV002542600	benign	Autoinflammatory syndrome	2022-03-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000755589	SCV002585201	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	NLRP3: BP4, BP7, BS1
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294025	SCV002587177	likely benign	Kidney disorder	2020-01-01	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000755589	SCV005260519	likely benign	not provided		criteria provided, single submitter	not provided
Unité médicale des maladies autoinflammatoires, CHRU Montpellier	RCV000084190	SCV000116323	not provided	Familial cold autoinflammatory syndrome 1		no assertion provided	not provided
PreventionGenetics, part of Exact Sciences	RCV004528782	SCV000310707	benign	NLRP3-related disorder	2019-03-06	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000249054	SCV001931446	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000755589	SCV001953000	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000755589	SCV001967810	likely benign	not provided		no assertion criteria provided	clinical testing