Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Immunology, |
RCV000604644 | SCV000583981 | likely pathogenic | Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency | criteria provided, single submitter | clinical testing | ||
Blueprint Genetics | RCV000788529 | SCV000927678 | uncertain significance | not provided | 2018-05-08 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000788529 | SCV001153272 | likely pathogenic | not provided | 2019-05-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000604644 | SCV001406450 | likely pathogenic | Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency | 2023-05-30 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Val40 amino acid residue in CTLA4. Other variant(s) that disrupt this residue have been observed in individuals with CTLA4-related conditions (PMID: 29729943, 30048690, 34111452), which suggests that this may be a clinically significant amino acid residue. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 430906). This missense change has been observed in individuals with CTLA4 haploinsufficiency (PMID: 28983403, 30048690, 34111452; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 40 of the CTLA4 protein (p.Val40Met). |