ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.1771C>G (p.Leu591Val) (rs767247726)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000463207 SCV000542148 uncertain significance Neurofibromatosis, type 1 2016-05-07 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 591 of the NF1 protein (p.Leu591Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. While this variant is present in population databases (rs767247726), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual 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. Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this rare sequence change is not predicted to affect protein function with respect to the missense amino acid substitution it encodes, but is predicted to affect splicing. 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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