ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4738G>A (p.Ala1580Thr) (rs754651519)

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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 RCV000570462 SCV000670369 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000471442 SCV000542069 uncertain significance Neurofibromatosis, type 1 2018-07-09 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1580 of the NF1 protein (p.Ala1580Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs754651519, ExAC 0.002%) but has not been reported in the literature in individuals with an NF1-related disease. 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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