ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.6665C>T (p.Thr2222Met)

gnomAD frequency: 0.00001  dbSNP: rs369803831
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166122 SCV000216893 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-18 criteria provided, single submitter clinical testing The p.T2222M variant (also known as c.6665C>T), located in coding exon 44 of the NF1 gene, results from a C to T substitution at nucleotide position 6665. The threonine at codon 2222 is replaced by methionine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs369803831. Based on data from the NHLBI Exome Sequencing Project (ESP), the T allele has an overall frequency of approximately 0.01% (1/13004) total alleles studied, having been observed in 0.02% (1/4404) African American alleles. To date, this alteration has been detected with an allele frequency of approximately 0.004% (greater than 110000 alleles tested) in our clinical cohort.This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis.Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000472540 SCV000542204 likely benign Neurofibromatosis, type 1 2024-01-07 criteria provided, single submitter clinical testing
GeneDx RCV001582655 SCV001818994 uncertain significance not provided 2020-05-20 criteria provided, single submitter clinical testing Reported in one control subject in a breast cancer case-control study, but was not observed in any of the cases (Momozawa 2018); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30287823)
Sema4, Sema4 RCV000166122 SCV002527663 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-07 criteria provided, single submitter curation
Genome-Nilou Lab RCV000472540 SCV002560981 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002372050 SCV002667209 likely benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-04-12 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 RCV002505211 SCV002814926 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2021-12-15 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.