Submissions for variant NM_001042492.3(NF1):c.279T>G (p.Cys93Trp)

dbSNP: rs1597629882

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001197025	SCV001367660	likely pathogenic	Neurofibromatosis, type 1	2020-03-18	criteria provided, single submitter	clinical testing	This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PM1,PM2,PM5,PP3.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001197025	SCV002247348	pathogenic	Neurofibromatosis, type 1	2024-05-15	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 93 of the NF1 protein (p.Cys93Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurofibromatosis, type 1 (PMID: 23668869, 23758643). ClinVar contains an entry for this variant (Variation ID: 930967). 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 95%. This variant disrupts the p.Cys93 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10862084, 17426081). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV001197025	SCV002561564	likely pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing