ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.6806G>A (p.Arg2269His)

gnomAD frequency: 0.00001  dbSNP: rs562367786
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132133 SCV000187204 uncertain significance Hereditary cancer-predisposing syndrome 2015-10-09 criteria provided, single submitter clinical testing The p.R2269H variant (also known as c.6806G>A), located in coding exon 45 of the NF1 gene, results from a G to A substitution at nucleotide position 6806. The arginine at codon 2269 is replaced by histidine, an amino acid with highly similar 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. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 110000 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 p.R2269H remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000474759 SCV000542038 likely benign Neurofibromatosis, type 1 2024-11-02 criteria provided, single submitter clinical testing
GeneDx RCV001582607 SCV001820397 uncertain significance not provided 2022-12-22 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in an individual with NF1, however no additional information was provided (Cali et al., 2017); Observed in individuals with breast cancer (Dorling et al., 2021); This variant is associated with the following publications: (PMID: 27838393, 33471991)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001582607 SCV002009292 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000132133 SCV002527669 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-17 criteria provided, single submitter curation
Genome-Nilou Lab RCV000474759 SCV002561003 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV003162591 SCV003895206 likely benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-12-21 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV005008041 SCV005639943 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2024-01-05 criteria provided, single submitter clinical testing

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