Submissions for variant NM_002351.5(SH2D1A):c.2T>C (p.Met1Thr)

dbSNP: rs2147519353

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001946671	SCV002236777	pathogenic	X-linked lymphoproliferative disease due to SH2D1A deficiency	2022-08-10	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1455661). Disruption of the initiator codon has been observed in individuals with X-linked lymphoproliferative syndrome (PMID: 22970278, 31415280). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the SH2D1A mRNA. There are no downstream in-frame methionine residues; therefore, it is expected to result in an absent or disrupted protein product. Loss-of-function variants in SH2D1A are known to be pathogenic (PMID: 9771704, 11049992, 15711562).
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002264437	SCV002542943	likely pathogenic	Autoinflammatory syndrome	2017-03-01	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV001946671	SCV002568243	pathogenic	X-linked lymphoproliferative disease due to SH2D1A deficiency	2022-06-21	criteria provided, single submitter	clinical testing	PVS1, PS4_Moderate, PM2