Submissions for variant NM_005045.4(RELN):c.3651C>G (p.Ile1217Met) (rs56342240)

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000173031	SCV000113138	likely benign	not specified	2014-09-10	criteria provided, single submitter	clinical testing
Genetic Services Laboratory,University of Chicago	RCV000173031	SCV000152497	likely benign	not specified	2017-01-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000173031	SCV000490765	uncertain significance	not specified	2016-12-02	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the RELN gene. The I1217M variant is observed in 298/66,736 (0.4%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I1217M variant 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 where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000081230	SCV000609270	likely benign	not provided	2020-02-01	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000081230	SCV000614866	benign	not provided	2019-01-07	criteria provided, single submitter	clinical testing
Invitae	RCV001083944	SCV000656287	likely benign	Norman-Roberts syndrome; Epilepsy, familial temporal lobe, 7	2019-12-31	criteria provided, single submitter	clinical testing
Mendelics	RCV000987939	SCV001137433	benign	Norman-Roberts syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000987939	SCV001323865	likely benign	Norman-Roberts syndrome	2017-05-09	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.