ClinVar Miner

Submissions for variant NM_004895.4(NLRP3):c.410G>A (p.Arg137His) (rs138946894)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000219739 SCV000278934 uncertain significance not provided 2016-07-19 criteria provided, single submitter clinical testing The R137H variant in the NLRP3 gene has been previously reported in two individuals with clinical findings consistent with a cryopyrin-associated periodic syndrome (Hernandez-Rodriguez et al., 2015; Lainka et al., 2010). However, this variant was also reported in another individual with lymphoma who was found to have an alternate molecular explanation for her features (Sharapova et al., 2016). Adidtionally, the NHLBI ESP Exome Sequencing Project reports R137H was observed in 5/8600 (0.06%) alleles from individuals of European American background, indicating it may be a rare benign variant in this population. The R137H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Furthermore, this substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. We interpret R137H as a variant of uncertain significance, which may be related to hepatosplenomegaly and lymphocyte infiltration.

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