ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3394C>T (p.Arg1132Cys)

gnomAD frequency: 0.00001  dbSNP: rs587781725
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129912 SCV000184730 uncertain significance Hereditary cancer-predisposing syndrome 2015-10-13 criteria provided, single submitter clinical testing The p.R1132C variant (also known as c.3394C>T), located in coding exon 26 of the NF1 gene, results from a C to T substitution at nucleotide position 3394. The arginine at codon 1132 is replaced by cysteine, an amino acid with highly dissimilar 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 0.01% (greater than 55000 alleles tested) in our clinical cohort.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 variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000474714 SCV000542101 uncertain significance Neurofibromatosis, type 1 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1132 of the NF1 protein (p.Arg1132Cys). This variant is present in population databases (rs587781725, gnomAD 0.01%). 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: 141407). 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.
GeneDx RCV001753513 SCV002005798 uncertain significance not provided 2023-08-01 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25486365, 2121369, 22807134, Martorana2022[CaseReport])
Genome-Nilou Lab RCV000474714 SCV002560291 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Medical Genetics, University of Parma RCV000474714 SCV002567764 uncertain significance Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV003162575 SCV003897070 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2020-12-23 criteria provided, single submitter clinical testing The c.3394C>T (p.R1132C) alteration is located in exon 26 (coding exon 26) of the NF1 gene. This alteration results from a C to T substitution at nucleotide position 3394, causing the arginine (R) at amino acid position 1132 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Laboratory of Medical Genetics Unit, Bambino Gesù Children's Hospital RCV003325187 SCV004012940 uncertain significance Astrocytoma IDH-mutant 2021-05-31 criteria provided, single submitter research

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