Submissions for variant NM_005045.4(RELN):c.4495G>C (p.Asp1499His)

gnomAD frequency: 0.00009  dbSNP: rs200428576

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000731945	SCV000617405	uncertain significance	not provided	2017-07-11	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the RELN gene. The D1499H variant has been reported previously in an individual with autism spectrum disorder; however, no further information was provided (Matsunami et al., 2014). The D1499H variant is observed in 17/66738 (0.03%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D1499H variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. However, 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	RCV000684890	SCV000812351	likely benign	Norman-Roberts syndrome; Familial temporal lobe epilepsy 7	2024-01-09	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000731945	SCV000859818	uncertain significance	not provided	2018-02-14	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000764663	SCV000895793	uncertain significance	Epilepsy, familial temporal lobe, 1; Norman-Roberts syndrome; Familial temporal lobe epilepsy 7	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001158968	SCV001320644	uncertain significance	Norman-Roberts syndrome	2017-04-27	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
New York Genome Center	RCV001263402	SCV001441445	uncertain significance	Autism	2019-05-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000731945	SCV004155685	uncertain significance	not provided	2022-08-01	criteria provided, single submitter	clinical testing