Submissions for variant NM_005045.4(RELN):c.1555G>T (p.Val519Phe) (rs560704715)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV000376559	SCV000465982	uncertain significance	Lissencephaly, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000439689	SCV000535177	uncertain significance	not provided	2016-12-21	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the RELN gene. The c.1555 G>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1555 G>T variant is observed in 118/16,500 (0.7%) alleles from individuals of South Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.1555 G>T may damage or destroy the natural acceptor site for intron 13 and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. If the c.1555 G>T variant does not alter splicing, it will result in the V519F missense change. The V519F variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV000439689	SCV000774910	likely benign	not provided	2019-02-26	criteria provided, single submitter	clinical testing