Total submissions: 7
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, |
RCV001821508 | SCV002067201 | uncertain significance | not specified | 2018-07-12 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000563538 | SCV002527504 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-18 | criteria provided, single submitter | curation | |
Genome- |
RCV000535878 | SCV002560289 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV002286748 | SCV002577262 | likely benign | not provided | 2022-09-27 | criteria provided, single submitter | clinical testing | See Variant Classification Assertion Criteria. |
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 |