ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2434A>C (p.Ile812Leu) (rs587781899)

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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 RCV000130236 SCV000185077 uncertain significance Hereditary cancer-predisposing syndrome 2015-12-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV000554294 SCV000628440 uncertain significance Neurofibromatosis, type 1 2018-11-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with leucine at codon 812 of the NF1 protein (p.Ile812Leu). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is present in population databases (rs587781899, ExAC 0.002%) but has not been reported in the literature in individuals with an NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 141640). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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