ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.47G>C (p.Arg16Pro)

dbSNP: rs1555594493
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002316643 SCV000666777 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2016-09-26 criteria provided, single submitter clinical testing The p.R16P variant (also known as c.47G>C), located in coding exon 1 of the NF1 gene, results from a G to C substitution at nucleotide position 47. The arginine at codon 16 is replaced by proline, an amino acid with dissimilar properties. This alteration has been detected in an individual with a clinical diagnosis of neurofibromatosis type 1 (Nemethova M et al. Ann. Hum. Genet., 2013 Sep;77:364-79). 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 5592 samples (11184 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles tested) in our clinical cohort. This amino acid position is conserved on limited sequence alignment. 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 RCV001212851 SCV001384452 uncertain significance Neurofibromatosis, type 1 2023-12-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 16 of the NF1 protein (p.Arg16Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurofibromatosis type 1 and childhood cancer (PMID: 23758643, 29489754). ClinVar contains an entry for this variant (Variation ID: 481953). 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.
Genome-Nilou Lab RCV001212851 SCV002561394 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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