Submissions for variant NM_001330078.2(NRXN1):c.2605C>A (p.Leu869Met)

gnomAD frequency: 0.00044  dbSNP: rs201818223

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723597	SCV000111399	uncertain significance	not provided	2013-03-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000723597	SCV000241892	likely benign	not provided	2021-02-09	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000188281	SCV000248282	uncertain significance	not specified	2015-06-24	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001085353	SCV000286214	benign	Pitt-Hopkins-like syndrome 2	2025-01-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001085353	SCV000431202	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.
Fulgent Genetics, Fulgent Genetics	RCV000515261	SCV000611416	uncertain significance	Pitt-Hopkins-like syndrome 2; Chromosome 2p16.3 deletion syndrome	2017-05-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316229	SCV000850741	uncertain significance	Inborn genetic diseases	2019-04-04	criteria provided, single submitter	clinical testing	The p.L909M variant (also known as c.2725C>A), located in coding exon 14 of the NRXN1 gene, results from a C to A substitution at nucleotide position 2725. The leucine at codon 909 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004537324	SCV004750083	benign	NRXN1-related disorder	2019-07-02	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).