ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2288T>C (p.Leu763Pro) (rs199474762)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165288 SCV000216006 pathogenic Hereditary cancer-predisposing syndrome 2016-03-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000220933 SCV000271252 likely pathogenic Neurofibromatosis, type 1 2015-07-30 criteria provided, single submitter clinical testing The p.Leu763Pro variant in NF1 has been reported in 2 individuals with Neurofibr omatosis type 1, with an apparently de novo occurence in one of these individual s (Fahsold 2000, Valero 2011). This variant was absent from large population stu dies. Computational prediction tools and conservation analysis do not provide st rong support for or against an impact to the protein. In summary, although addit ional studies are required to fully establish its clinical significance, the p.L eu763Pro variant is likely pathogenic.
Invitae RCV000220933 SCV000628428 likely pathogenic Neurofibromatosis, type 1 2017-04-28 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 763 of the NF1 protein (p.Leu763Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals and a family affected with neurofibromatosis type 1 in the literature (PMID: 10712197, 16005615, 21354044) and in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 68312). 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: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change that has been described in several affected individuals. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
UniProtKB/Swiss-Prot RCV000059164 SCV000090693 not provided not provided no assertion provided not provided

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