ClinVar Miner

Submissions for variant NM_001243133.2(NLRP3):c.1937A>G (p.Asp646Gly)

gnomAD frequency: 0.00001  dbSNP: rs1342790456
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001329328 SCV001520734 uncertain significance Chronic infantile neurological, cutaneous and articular syndrome 2020-03-20 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV003759045 SCV004458794 uncertain significance Cryopyrin associated periodic syndrome 2023-10-05 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 648 of the NLRP3 protein (p.Asp648Gly). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with NLRP3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1028307). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NLRP3 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.
Ambry Genetics RCV004035671 SCV004990024 likely benign Inborn genetic diseases 2023-10-27 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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