ClinVar Miner

Submissions for variant NM_004895.4(NLRP3):c.680C>T (p.Ala227Val) (rs180177493)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000217712 SCV000278936 uncertain significance not provided 2018-06-07 criteria provided, single submitter clinical testing The A227V variant has been reported, using alternative nomenclature, in an individual with rheumatoid arthritis, high leukocyte count and recurrent fever (Verma et al., 2008). The variant is observed in 53/25786 (0.2055%) alleles from individuals of Finnish background in large population cohorts (Lek et al., 2016). The variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. However, the variant is located in the NACHT domain, which is the major locus of CAPS-associated pathogenic variants (Masters et al., 2009). In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001078842 SCV000767332 likely benign Cryopyrin associated periodic syndrome 2019-12-31 criteria provided, single submitter clinical testing
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000084227 SCV000116362 not provided Familial cold urticaria no assertion provided not provided

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