Submissions for variant NM_001243133.2(NLRP3):c.146A>G (p.His49Arg)

gnomAD frequency: 0.00001  dbSNP: rs367663649

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000726996	SCV000618028	uncertain significance	not provided	2017-07-28	criteria provided, single submitter	clinical testing	The H51R variant has been reported previosuly as a variant of uncertain significance in association with CAPS (Hernández-Rodríguez et al., 2015). The variant is observed in 1/10340 (0.01%) alleles from individuals of African background in the ExAC dataset (Lek et al., 2016). H51R is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Eurofins Ntd Llc (ga)	RCV000726996	SCV000704803	uncertain significance	not provided	2016-12-21	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000726996	SCV001715675	uncertain significance	not provided	2020-07-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003593979	SCV004292028	likely benign	Cryopyrin associated periodic syndrome	2023-12-20	criteria provided, single submitter	clinical testing