Submissions for variant NM_001167.4(XIAP):c.1457_1458del (p.Thr486fs)

dbSNP: rs2053561076

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001319322	SCV001510062	uncertain significance	X-linked lymphoproliferative disease due to XIAP deficiency	2020-10-04	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 sequence change results in a frameshift in the XIAP gene (p.Thr486Serfs*14). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 12 amino acid(s) of the XIAP protein and extend the protein by an additional 1 amino acid(s). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with XIAP-related conditions. This variant disrupts the C-terminus of the XIAP protein. Other variant(s) that disrupt this region (p.Gln492* or p.Q492X) have been observed in individuals with XIAP-related conditions (PMID: 27815752). This suggests that this may be a clinically significant region of the protein.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV001319322	SCV002512325	uncertain significance	X-linked lymphoproliferative disease due to XIAP deficiency	2022-01-26	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1 moderate, PM2 moderate