Submissions for variant NM_001042492.3(NF1):c.5167C>G (p.Gln1723Glu)

gnomAD frequency: 0.00001  dbSNP: rs766727694

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002319402	SCV001185450	uncertain significance	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2021-03-09	criteria provided, single submitter	clinical testing	The p.Q1702E variant (also known as c.5104C>G), located in coding exon 36 of the NF1 gene, results from a C to G substitution at nucleotide position 5104. The glutamine at codon 1702 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV001247079	SCV001420481	uncertain significance	Neurofibromatosis, type 1	2023-11-05	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1702 of the NF1 protein (p.Gln1702Glu). This variant is present in population databases (rs766727694, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 825451). 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 NF1 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003238270	SCV002011205	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001023551	SCV002527603	uncertain significance	Hereditary cancer-predisposing syndrome	2021-08-31	criteria provided, single submitter	curation
Genome-Nilou Lab	RCV001247079	SCV002560515	uncertain significance	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing