Submissions for variant NM_000448.3(RAG1):c.2564A>G (p.Asn855Ser)

dbSNP: rs199474690

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000480355	SCV000565476	likely pathogenic	not provided	2014-08-13	criteria provided, single submitter	clinical testing	To our knowledge, the N855S variant has neither been published as pathogenic, nor reported as a benign polymorphism. This variant was not observed in approximately 6500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. N855S is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is highly conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in the same and nearby residues (N855I, R841Q, R841W) have been reported in the Human Gene Mutation Database in association with RAG1-deficiency disorders (Stenson et al., 2009), supporting the functional importance of this region of the protein. Therefore, this is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.
Revvity Omics, Revvity	RCV000480355	SCV004236538	uncertain significance	not provided	2023-08-03	criteria provided, single submitter	clinical testing