rs1494558, also known as Thr66Ile and Ile66Thr, is a variant in the IL7R interleukin 7 receptor gene. This SNP is unusual in being in "minus" orientation (relative to the reference genome). It is also a SNP in which the more common allele varies depending on the population; rs1494558(G) is generally more common in Caucasian populations, while rs1494558(A) is often more common in Asian populations. The (G) allele, on the minus strand, corresponds to the Thr codon, and the (A) allele corresponds to the Ile codon.
It is unclear if this SNP, either on it's own or together with rs1494555, is associated with risk for an autosomal recessive form (T-B+NK+) of severe combined immunodeficiency (SCID), as reported in both OMIM and ClinVar. An article published in 1998 ([PMID 9843216] described a single T-B+NK+ SCID patient shown by sequencing to carry rs1494558(A;A) and rs1494555(C;C) genotypes. This patient produced no IL7R mRNA (or protein), whereas his parents, who were both heterozygous at both SNPs, did and showed no SCID-associated phenotypes.
The authors conclude that this patient has a pair of defective IL7R alleles, however, "it remains to be determined if these amino acid changes are in fact disease-causing defects".[PMID 9843216] Given that neither SNP is particularly rare if enough populations are surveyed, whereas IL7R-deficient forms of SCID are quite rare (perhaps 1 in 500,000 births, based on CDC estimates), it seems quite likely that the causative mutation(s) leading to the defective IL7R alleles in the patient described in 1998 remain to be discovered and that they are not rs1494558 or rs1494555.
|Desc||SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-POSITIVE, NK CELL-POSITIVE|
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