ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3374C>T (p.Ala1125Val)

gnomAD frequency: 0.00002  dbSNP: rs902739109
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000535878 SCV000628513 uncertain significance Neurofibromatosis, type 1 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1125 of the NF1 protein (p.Ala1125Val). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of NF1-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 457644). 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) performed at Invitae indicates that this missense variant is not expected to disrupt NF1 protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV002314930 SCV000663240 likely benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2023-02-13 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Genetic Services Laboratory, University of Chicago RCV001821508 SCV002067201 uncertain significance not specified 2018-07-12 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000563538 SCV002527504 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-18 criteria provided, single submitter curation
Genome-Nilou Lab RCV000535878 SCV002560289 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
GeneDx RCV002286748 SCV002577262 likely benign not provided 2022-09-27 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
Fulgent Genetics, Fulgent Genetics RCV002483371 SCV002786334 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2021-11-01 criteria provided, single submitter clinical testing

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