ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2288T>G (p.Leu763Arg) (rs199474762)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222376 SCV000274651 likely pathogenic Hereditary cancer-predisposing syndrome 2015-03-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Well-characterized mutation at same position,Other strong data supporting pathogenic classification,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Center for Human Genetics, Inc RCV000196515 SCV000781944 likely pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000196515 SCV000254486 uncertain significance Neurofibromatosis, type 1 2015-02-20 criteria provided, single submitter clinical testing This sequence change replaces leucine with arginine at codon 763 of the NF1 protein (p.Leu763Arg). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and arginine. This variant has not been published in the literature and is not present in population databases. 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"). A different missense substitution at this codon (p.Leu763Pro) has been reported in an individual with neurofibromatosis type 1 (PMID: 10712197). However, the functional and clinical significance of the p.Leu763Pro missense change is uncertain. In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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