Submissions for variant NM_001042492.3(NF1):c.8490C>A (p.Phe2830Leu)

gnomAD frequency: 0.00004  dbSNP: rs760550772

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166910	SCV000217728	uncertain significance	Hereditary cancer-predisposing syndrome	2015-07-29	criteria provided, single submitter	clinical testing	The p.F2830L variant (also known as c.8490C>A), located in coding exon 58 of the NF1 gene, results from a C to A substitution at nucleotide position 8490. The phenylalanine at codon 2830 is replaced by leucine, an amino acid with highly similar 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 0.005% (greater than 110000 alleles tested) in our clinical cohort. 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 p.F2830L remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000232715	SCV000284531	likely benign	Neurofibromatosis, type 1	2025-01-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000681318	SCV000808780	uncertain significance	not provided	2023-11-21	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Sema4, Sema4	RCV000166910	SCV002528152	uncertain significance	Hereditary cancer-predisposing syndrome	2021-11-27	criteria provided, single submitter	curation
Genome-Nilou Lab	RCV000232715	SCV002561527	uncertain significance	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003162713	SCV003896950	likely benign	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2023-03-08	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.