Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001058070 | SCV001222609 | uncertain significance | Periodic fever-infantile enterocolitis-autoinflammatory syndrome; Familial cold autoinflammatory syndrome 4 | 2019-12-03 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs199475957, ExAC 0.04%). This sequence change replaces asparagine with serine at codon 604 of the NLRC4 protein (p.Asn604Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NLRC4-related conditions. ClinVar contains an entry for this variant (Variation ID: 103075). |
Human Evolutionary Genetics, |
RCV000089335 | SCV000121792 | untested | not provided | no assertion provided | not provided | Converted during submission to not provided. |