Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000821949 | SCV000962723 | uncertain significance | Immunodeficiency 14 | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 774 of the PIK3CD protein (p.Val774Met). This variant is present in population databases (rs370932461, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with PIK3CD-related conditions. ClinVar contains an entry for this variant (Variation ID: 663967). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
ARUP Laboratories, |
RCV000821949 | SCV001159783 | uncertain significance | Immunodeficiency 14 | 2018-07-09 | criteria provided, single submitter | clinical testing | The PIK3CD c.2320G>A; p.Val774Met variant (rs370932461), to our knowledge, is not reported in the medical literature or in gene-specific databases, but is observed in the general population at an overall frequency of 0.0033% (9/273466 alleles) in the Genome Aggregation Database. The valine at codon 774 is moderately conserved, but computational algorithms (PolyPhen-2: benign, SIFT: damaging) predict conflicting effects of this variant on protein structure/function. Due to the lack of clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty. |