Submissions for variant NM_001330078.2(NRXN1):c.4392T>C (p.His1464=)

gnomAD frequency: 0.00035  dbSNP: rs112536447

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127237	SCV000170792	benign	not specified	2013-10-07	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina	RCV000649752	SCV000431183	uncertain significance	Pitt-Hopkins-like syndrome 2	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genetic Services Laboratory, University of Chicago	RCV000127237	SCV000596058	likely benign	not specified	2016-10-14	criteria provided, single submitter	clinical testing
Invitae	RCV000649752	SCV000771584	likely benign	Pitt-Hopkins-like syndrome 2	2024-01-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000717146	SCV000847993	likely benign	History of neurodevelopmental disorder	2016-10-11	criteria provided, single submitter	clinical testing	Synonymous alterations with insufficient evidence to classify as benign
CeGaT Center for Human Genetics Tuebingen	RCV003407536	SCV004146117	likely benign	not provided	2022-05-01	criteria provided, single submitter	clinical testing	NRXN1: BP4, BP7