ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4766C>T (p.Thr1589Met)

gnomAD frequency: 0.00001  dbSNP: rs185660700
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000195487 SCV000254503 likely benign Neurofibromatosis, type 1 2025-01-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV000213390 SCV000275473 uncertain significance Hereditary cancer-predisposing syndrome 2015-12-10 criteria provided, single submitter clinical testing The p.T1589M variant (also known as c.4766C>T), located in coding exon 36 of the NF1 gene, results from a C to T substitution at nucleotide position 4766. The threonine at codon 1589 is replaced by methionine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs185660700. Based on data from the 1000 Genomes Project, the T allele has an overall frequency of approximately 0.05% (1/2098) total alleles studied. The highest observed frequency was 0.94% (1/106) African-American SW alleles. This variant was not reported in the NHLBI Exome Sequencing Project (ESP) population-based cohort.To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 110000alleles tested) in our clinical cohort.This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis.Since supporting evidence is limited at this time, the clinical significance of p.T1589Mremains unclear.
PreventionGenetics, part of Exact Sciences RCV000679395 SCV000806286 uncertain significance not provided 2017-05-30 criteria provided, single submitter clinical testing
GeneDx RCV000679395 SCV000808483 uncertain significance not provided 2022-11-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in individuals with breast cancer (Momozawa 2018); This variant is associated with the following publications: (PMID: 30287823)
Fulgent Genetics, Fulgent Genetics RCV000764113 SCV000895081 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2022-05-31 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000213390 SCV002527584 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-21 criteria provided, single submitter curation
Genome-Nilou Lab RCV000195487 SCV002560464 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV003165467 SCV003899271 likely benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2023-01-11 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000679395 SCV004565108 uncertain significance not provided 2023-05-03 criteria provided, single submitter clinical testing The NF1 c.4766C>T; p.Thr1589Met variant (rs185660700), is reported in the literature in individuals affected with breast cancer but is also found in controls (Momozawa 2018). This variant is reported in ClinVar (Variation ID: 216405) and is found in the general population with an overall allele frequency of 0.0025% (7/282,338 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.318). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Momozawa Y et al. Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. Nat Commun. 2018 Oct 4;9(1):4083. PMID: 30287823.

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.