Submissions for variant NM_001330078.2(NRXN1):c.1365T>C (p.Leu455=)

gnomAD frequency: 0.00051  dbSNP: rs201727684

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000186641	SCV000170795	benign	not specified	2013-01-14	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.
Eurofins Ntd Llc (ga)	RCV000723784	SCV000203145	uncertain significance	not provided	2016-07-12	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004528847	SCV000306816	likely benign	NRXN1-related disorder	2021-01-04	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Illumina Laboratory Services, Illumina	RCV001084654	SCV000431207	uncertain significance	Pitt-Hopkins-like syndrome 2	2018-01-12	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.
Invitae	RCV001084654	SCV000562376	likely benign	Pitt-Hopkins-like syndrome 2	2024-01-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000186641	SCV000596069	likely benign	not specified	2017-05-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002312908	SCV000847606	likely benign	Inborn genetic diseases	2016-08-22	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000723784	SCV001746358	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	NRXN1: BP4, BP7