Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001214883 | SCV001386589 | uncertain significance | Sterile multifocal osteomyelitis with periostitis and pustulosis | 2022-09-19 | 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 169 of the IL1RN protein (p.Val169Ile). This variant is present in population databases (rs143208167, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with IL1RN-related conditions. ClinVar contains an entry for this variant (Variation ID: 944477). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
Center for Genomics, |
RCV003224528 | SCV003920063 | uncertain significance | Microvascular complications of diabetes, susceptibility to, 4; Sterile multifocal osteomyelitis with periostitis and pustulosis; Gastric cancer | 2021-03-30 | criteria provided, single submitter | clinical testing | IL1RN NM_173841.2 exon 6 p.Val169Ile (c.505G>A): This variant has not been reported in the literature but is present in 0.02% (5/24970) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/2-113890410-G-A). This variant amino acid Isoleucine (Ile) is present in 9 species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |