ClinVar Miner

Submissions for variant NM_004895.4(NLRP3):c.584C>T (p.Thr195Met) (rs76291085)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000761714 SCV000278955 uncertain significance not provided 2014-05-15 criteria provided, single submitter clinical testing The T195M variant has not been published as a mutation in association with periodic fever syndrome, nor has it been reported as a benign polymorphism to our knowledge. This variant has been observed in a patient with Behcet's syndrome, a systemic inflammatory disorder (Yuksel et al., 2014). The T195M variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T195M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is variably conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000761714 SCV000891897 uncertain significance not provided 2018-07-01 criteria provided, single submitter clinical testing
Invitae RCV001070393 SCV001235620 uncertain significance Cryopyrin associated periodic syndrome 2019-11-27 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 195 of the NLRP3 protein (p.Thr195Met). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs76291085, ExAC 0.02%). This variant has been observed in an individual affected with Beh et s syndrome (PMID: 24135410). ClinVar contains an entry for this variant (Variation ID: 234297). This variant has been reported to have conflicting or insufficient data to determine the effect on NLRP3 protein function (PMID: 24135410). 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.

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