Submissions for variant NM_000080.4(CHRNE):c.1183T>G (p.Phe395Val)

gnomAD frequency: 0.00011  dbSNP: rs755802710

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000324705	SCV000341863	uncertain significance	not provided	2016-06-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000795701	SCV000935171	uncertain significance	Congenital myasthenic syndrome 4A	2024-01-22	criteria provided, single submitter	clinical testing	This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 395 of the CHRNE protein (p.Phe395Val). This variant is present in population databases (rs755802710, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CHRNE-related conditions. ClinVar contains an entry for this variant (Variation ID: 287916). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CHRNE protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Laboratory Services, Illumina	RCV001122285	SCV001280998	uncertain significance	Congenital myasthenic syndrome	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.
Revvity Omics, Revvity	RCV000324705	SCV003833689	uncertain significance	not provided	2019-09-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004021235	SCV004923578	uncertain significance	Inborn genetic diseases	2023-09-29	criteria provided, single submitter	clinical testing	The c.1183T>G (p.F395V) alteration is located in exon 10 (coding exon 10) of the CHRNE gene. This alteration results from a T to G substitution at nucleotide position 1183, causing the phenylalanine (F) at amino acid position 395 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Breakthrough Genomics, Breakthrough Genomics	RCV000324705	SCV005192455	uncertain significance	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001122285	SCV001459088	uncertain significance	Congenital myasthenic syndrome	2019-10-28	no assertion criteria provided	clinical testing