ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.7520C>T (p.Thr2507Ile)

gnomAD frequency: 0.00006  dbSNP: rs149055633
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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 RCV000130522 SCV000185391 likely benign Hereditary cancer-predisposing syndrome 2015-12-05 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;in silico models in agreement (benign);Insufficient or Conflicting Evidence;Rarity in general population databases (dbSNP, ESP, 1000 Genomes)
GeneDx RCV000421743 SCV000521069 likely benign not provided 2020-05-18 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 10712197, 18041031)
Labcorp Genetics (formerly Invitae), Labcorp RCV000475666 SCV000542110 likely benign Neurofibromatosis, type 1 2025-01-29 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000421743 SCV000806317 uncertain significance not provided 2017-08-23 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000764117 SCV000895085 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2018-10-31 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001818315 SCV002066719 uncertain significance not specified 2020-12-10 criteria provided, single submitter clinical testing DNA sequence analysis of the NF1 gene demonstrated a sequence change, c.7457C>T, in exon 50 that results in an amino acid change, p.Thr2486Ile. This sequence change has been described in the gnomAD database with a frequency of 0.012% in the European sub-population (dbSNP rs149055633). The p.Thr2486Ile change has been described in individuals with neurofibromatosis type 1 (PMID: 10712197). The p.Thr2486Ile change affects a poorly conserved amino acid residue located in a domain of the NF1 protein that is known to be functional. The p.Thr2486Ile substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Thr2486Ile change remains unknown at this time.
Ambry Genetics RCV002381447 SCV002674599 likely benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2020-06-05 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000421743 SCV005624656 uncertain significance not provided 2023-10-20 criteria provided, single submitter clinical testing

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