Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Ophthalmology, |
RCV000850251 | SCV000891105 | pathogenic | Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency | 2019-03-15 | criteria provided, single submitter | research | |
Invitae | RCV000850251 | SCV001495321 | uncertain significance | Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency | 2020-03-31 | criteria provided, single submitter | clinical testing | 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. This variant has been reported to affect CTLA4 protein function (PMID: 29375547). This variant has been observed in individual(s) with clinical features of CTLA4 haploinsufficiency (PMID: 29375547, 31396201). ClinVar contains an entry for this variant (Variation ID: 623475). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 139 of the CTLA4 protein (p.Tyr139Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. |
Ce |
RCV001311982 | SCV001502380 | pathogenic | not provided | 2020-12-01 | criteria provided, single submitter | clinical testing | |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000850251 | SCV002073326 | likely pathogenic | Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency | criteria provided, single submitter | clinical testing | The missense variant p.Y139C in CTLA4 (NM_005214.5) has been previously reported in affected patients (Siggs OM et al; Sic H et al). It has been submitted to ClinVar with conflicting interpretations of pathogenicity (Likely Pathogenic and Uncertain Significance). The p.Y139C variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.Y139C missense variant is predicted to be damaging by both SIFT and PolyPhen2. The tyrosine residue at codon 139 of CTLA4 is conserved in all mammalian species. The nucleotide c.416 in CTLA4 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic. |