ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.3748C>T (p.Arg1250Trp) (rs1452005208)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570364 SCV000663013 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000541317 SCV000628542 uncertain significance Neurofibromatosis, type 1 2018-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1250 of the NF1 protein (p.Arg1250Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 457665). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably 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.
