ClinVar Miner

Submissions for variant NM_033004.4(NLRP1):c.197C>T (p.Ala66Val) (rs1057519493)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479210 SCV000573522 likely pathogenic not provided 2017-02-27 criteria provided, single submitter clinical testing The A66V variant in the NLRP1 gene has been reported previously in the heterozygous state in a family with MSPC (Zhong et al., 2016). The A66V variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A66V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. While this substitution occurs at a position that is not conserved across species, it is located in the auto-inhibitory pyrin domain (Zhong et al., 2016). Functional studies indicate that cells overexpressing A66V have significantly increased inflammosome assembly compared to wild type, and A66V leads to a disruption in proper protein folding (Zhong et al., 2016). The A66V variant is a strong candidate for a pathogenic variant.
OMIM RCV000416502 SCV000494292 pathogenic Palmoplantar carcinoma, multiple self-healing 2019-09-30 no assertion criteria provided literature only

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