ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4195T>C (p.Ser1399Pro) (rs1555618533)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000537009 SCV000628576 uncertain significance Neurofibromatosis, type 1 2017-02-22 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 1399 of the NF1 protein (p.Ser1399Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant and a silent sequence change on the same allele have been shown to arise de novo in an individual affected with neurofibromatosis type 1 (PMID: 17311297). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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