Submissions for variant NM_001243133.2(NLRP3):c.2107C>A (p.Gln703Lys)

gnomAD frequency: 0.03262  dbSNP: rs35829419

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000246002	SCV000310709	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000282807	SCV000356977	benign	Familial cold autoinflammatory syndrome 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV000340224	SCV000356978	benign	Chronic infantile neurological, cutaneous and articular syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV000394881	SCV000356979	benign	Familial amyloid nephropathy with urticaria AND deafness	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000416176	SCV000493426	benign	not provided	2022-03-01	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000246002	SCV000539915	benign	not specified	2019-01-22	criteria provided, single submitter	clinical testing	The p.Gln705Lys variant in NLRP3 is classified as benign because it has been identified in 3.8% (10781/280716) of total chromosomes, including 266 homozygotes, by gnomAD (http://gnomad.broadinstitute.org). Although this variant has been reported in association with autoimmune or inflammatory conditions, several studies have shown equal frequency in cases and ethnically matched controls (Jenko 2016, Lidar 2017, Naselli 2016, Yang 2017). ACMG/AMP criteria: BA1.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000416176	SCV000604550	benign	not provided	2023-11-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000531876	SCV000646265	benign	Cryopyrin associated periodic syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000416176	SCV001144770	benign	not provided	2018-12-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000416176	SCV001752083	benign	not provided	2019-01-16	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32477355, 26178285, 32199921, 22843550, 30245029, 29148409, 28638818, 28692792, 29977033, 29265930, 30140708, 29610014, 27576327, 29770580, 23215645, 29850521, 29230505, 22128899, 17509468, 22529966, 28028683, 26020059, 27036377, 27943647, 26848126, 27884173, 22403613, 22995991, 20182451, 25596455, 22935299, 18311798, 21245836, 19319132, 20981092, 29097263, 29500522, 30447690, 30536174)
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262891	SCV002543634	benign	Autoinflammatory syndrome	2022-02-10	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000416176	SCV002568170	uncertain significance	not provided	2022-06-01	criteria provided, single submitter	clinical testing	PS3, BS1, BP4
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294151	SCV002587265	benign	Focal segmental glomerulosclerosis	2022-09-02	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000246002	SCV001744269	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000246002	SCV001932757	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000246002	SCV001954109	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000246002	SCV001972988	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000416176	SCV002036408	likely benign	not provided		no assertion criteria provided	clinical testing