ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2294G>A (p.Arg765His) (rs199474777)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000221393 SCV000277121 uncertain significance Hereditary cancer-predisposing syndrome 2015-07-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype,Insufficient or conflicting evidence,Other data supporting benign classification
Center for Human Genetics, Inc RCV000197680 SCV000781945 uncertain significance Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
GeneDx RCV000059165 SCV000808282 likely benign not provided 2018-06-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000197680 SCV000254487 uncertain significance Neurofibromatosis, type 1 2018-05-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 765 of the NF1 protein (p.Arg765His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs199474777, ExAC 0.07%). This variant has been reported in individuals affected with neurofibromatosis and ovarian cancer (PMID: 10336779, 24448499). However, in the neurofibromatosis family, the variant did not segregate with disease and was absent in two affected children of the proband (PMID: 10336779). ClinVar contains an entry for this variant (Variation ID: 68313). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
SIB Swiss Institute of Bioinformatics RCV000197680 SCV000803602 uncertain significance Neurofibromatosis, type 1 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Uncertain Significance - Insufficient Evidence, for Neurofibromatosis 1, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder.
UniProtKB/Swiss-Prot RCV000059165 SCV000090694 not provided not provided no assertion provided not provided

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