Submissions for variant NM_001042492.3(NF1):c.1541A>C (p.Gln514Pro)

gnomAD frequency: 0.00001  dbSNP: rs775369084

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000222304	SCV000277247	uncertain significance	Hereditary cancer-predisposing syndrome	2015-07-16	criteria provided, single submitter	clinical testing	The p.Q514P variant (also known as c.1541A>C), located in coding exon 14 of the NF1 gene, results from an A to C substitution at nucleotide position 1541. The glutamine at codon 514 is replaced by proline, an amino acid with somesimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position.To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 55000alleles tested) in our clinical cohort.This amino acid position is well 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 p.Q514Premains unclear.
Invitae	RCV000233491	SCV000284385	likely benign	Neurofibromatosis, type 1	2024-01-28	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000233491	SCV000781916	likely benign	Neurofibromatosis, type 1	2016-11-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001555550	SCV001776989	likely benign	not provided	2020-12-07	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002399792	SCV002705077	likely benign	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2019-03-19	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001555550	SCV004222154	benign	not provided	2021-07-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004547555	SCV004729618	likely benign	NF1-related disorder	2019-09-11	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).