Submissions for variant NM_001042492.3(NF1):c.8084C>T (p.Pro2695Leu)

dbSNP: rs2070328290

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001059067	SCV001223672	uncertain significance	Neurofibromatosis, type 1	2024-04-30	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2674 of the NF1 protein (p.Pro2674Leu). 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: 854100). 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 expected to disrupt NF1 protein function with a positive predictive value of 80%. 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	RCV003160476	SCV003861120	uncertain significance	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2023-02-01	criteria provided, single submitter	clinical testing	The p.P2674L variant (also known as c.8021C>T), located in coding exon 54 of the NF1 gene, results from a C to T substitution at nucleotide position 8021. The proline at codon 2674 is replaced by leucine, an amino acid with 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.
Baylor Genetics	RCV003467797	SCV004198283	uncertain significance	Juvenile myelomonocytic leukemia	2023-10-03	criteria provided, single submitter	clinical testing
GenomeConnect - Invitae Patient Insights Network	RCV003483770	SCV004228556	not provided	Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 05-02-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.