ClinVar Miner

Submissions for variant NM_001199138.2(NLRC4):c.2728G>A (p.Val910Ile)

gnomAD frequency: 0.00003  dbSNP: rs144418059
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000793887 SCV000933265 uncertain significance Periodic fever-infantile enterocolitis-autoinflammatory syndrome; Familial cold autoinflammatory syndrome 4 2023-11-07 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 910 of the NLRC4 protein (p.Val910Ile). This variant is present in population databases (rs144418059, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with NLRC4-related conditions. ClinVar contains an entry for this variant (Variation ID: 640786). 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 NLRC4 protein function with a negative predictive value of 80%. 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.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV002468606 SCV002762842 uncertain significance Familial cold autoinflammatory syndrome 4 2022-12-01 criteria provided, single submitter clinical testing A heterozygous missense variation in exon 8 of the NLRC4 gene that results in the amino acid substitution of Isoleucine for Valine at codon 910 (p.Val910Ile) was detected. This variant has not been reported in the gnomAD and 1000 genomes databases.The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as pathogenic. In summary, the variant meets our criteria to be classified as a variant of uncertain significance.

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