ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.40G>T (p.Val14Phe)

dbSNP: rs2143145306
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002023004 SCV002305204 uncertain significance Neurofibromatosis, type 1 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 14 of the NF1 protein (p.Val14Phe). This variant is not present in population databases (gnomAD no frequency). 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: 1512400). 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) performed at Invitae indicates that this missense variant is not expected to disrupt NF1 protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV002324487 SCV002632379 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-02-12 criteria provided, single submitter clinical testing The p.V14F variant (also known as c.40G>T), located in coding exon 1 of the NF1 gene, results from a G to T substitution at nucleotide position 40. The valine at codon 14 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV002023004 SCV004031192 uncertain significance Neurofibromatosis, type 1 2023-06-20 criteria provided, single submitter clinical testing The NF1 c.40G>T (p.Val14Phe) missense change is absent in gnomAD v2.1.1 ( The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Neurofibromatosis type 1. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

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