Submissions for variant NM_144687.4(NLRP12):c.2830C>T (p.Arg944Trp)

dbSNP: rs104895570

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	RCV000736056	SCV000864268	likely benign	not specified	2017-10-27	criteria provided, single submitter	clinical testing	BS1, BP4; This alteration has an allele frequency that is greater than expected for the associated disease, and is predicted to be tolerated by multiple functional prediction tools.
Invitae	RCV001047694	SCV001211672	uncertain significance	Familial cold autoinflammatory syndrome 2	2024-01-22	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 944 of the NLRP12 protein (p.Arg944Trp). This variant is present in population databases (rs104895570, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. ClinVar contains an entry for this variant (Variation ID: 599430). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The tryptophan amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263961	SCV002543601	likely benign	Autoinflammatory syndrome	2021-04-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003258958	SCV003956398	uncertain significance	Inborn genetic diseases	2023-04-04	criteria provided, single submitter	clinical testing	The c.2830C>T (p.R944W) alteration is located in exon 8 (coding exon 8) of the NLRP12 gene. This alteration results from a C to T substitution at nucleotide position 2830, causing the arginine (R) at amino acid position 944 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV003311884	SCV004011098	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	NLRP12: BP4