Submissions for variant NM_001330078.2(NRXN1):c.1945A>G (p.Ile649Val)

gnomAD frequency: 0.00062  dbSNP: rs200074974

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723794	SCV000203142	uncertain significance	not provided	2015-09-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000723794	SCV000241837	likely benign	not provided	2021-02-16	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000188230	SCV000248276	uncertain significance	not specified	2014-12-16	criteria provided, single submitter	clinical testing
Invitae	RCV000649744	SCV000771576	benign	Pitt-Hopkins-like syndrome 2	2024-01-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316970	SCV000851237	likely benign	Inborn genetic diseases	2021-09-22	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	RCV000723794	SCV001152307	uncertain significance	not provided	2016-07-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000649744	SCV001304009	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.
Baylor Genetics	RCV000649744	SCV001529577	uncertain significance	Pitt-Hopkins-like syndrome 2	2018-04-08	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
PreventionGenetics, part of Exact Sciences	RCV004532729	SCV004746756	uncertain significance	NRXN1-related disorder	2024-02-21	criteria provided, single submitter	clinical testing	The NRXN1 c.2065A>G variant is predicted to result in the amino acid substitution p.Ile689Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.12% of alleles in individuals of European (Non-Finnish) descent in gnomAD, which is likely too common to be an unreported cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000723794	SCV001799555	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000723794	SCV001975918	likely benign	not provided		no assertion criteria provided	clinical testing