ClinVar Miner

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

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Total submissions: 3
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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

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