Submissions for variant NM_001167.4(XIAP):c.1317_1318delinsAT (p.Gln440Ter)

dbSNP: rs2148112156

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002006209	SCV002274052	likely pathogenic	X-linked lymphoproliferative disease due to XIAP deficiency	2021-03-08	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 C-terminus of the XIAP protein. Other variant(s) that disrupt this region (p.Gly466*, p.Gln492*, p.Phe462Leufs*7) have been observed in individuals with XIAP-related conditions (PMID: 21543760, 27815752, 23973892). This suggests that this may be a clinically significant region of the protein. This variant has not been reported in the literature in individuals with XIAP-related conditions. The frequency data for this variant in the population databases is not available, as this variant may be reported as separate entries in the ExAC database. This sequence change creates a premature translational stop signal (p.Gln440*) in the XIAP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 58 amino acid(s) of the XIAP protein.