Submissions for variant NM_001243133.2(NLRP3):c.944C>T (p.Pro315Leu)

gnomAD frequency: 0.00010  dbSNP: rs180177462

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000213159	SCV000279569	uncertain significance	not provided	2022-03-07	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as p.P315L; Reported previously using alternate nomenclature P315L in a patient with clinical suspicion for Muckle-Wells syndrome, however familial segregation information and in vitro functional studies were not included (Wakhlu et al., 2015); This variant is associated with the following publications: (PMID: 31325311, 26218404, 19302049, 33329557, 32082075)
Illumina Laboratory Services, Illumina	RCV000378566	SCV000356933	likely 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000084253	SCV000356934	likely 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000344447	SCV000356935	likely 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). 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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV001195579	SCV001365974	likely benign	not specified	2019-05-24	criteria provided, single submitter	clinical testing	The p.Pro317Leu variant in NLRP3 is classified as likely benign because it has been identified in 0.059% (18/31012) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that the p.Pro317Leu variant may not impact the protein. ACMG/AMP Criteria applied: BS1, BP4.
Invitae	RCV001226114	SCV001398414	likely benign	Cryopyrin associated periodic syndrome	2024-01-08	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262700	SCV002542652	uncertain significance	Autoinflammatory syndrome	2016-12-16	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294026	SCV002587146	uncertain significance	Kidney disorder	2016-12-12	criteria provided, single submitter	clinical testing
Unité médicale des maladies autoinflammatoires, CHRU Montpellier	RCV000084253	SCV000116389	not provided	Familial cold autoinflammatory syndrome 1		no assertion provided	not provided