ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4074_4075delinsAA (p.Pro1359Thr) (rs1555617362)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000552219 SCV000628566 uncertain significance Neurofibromatosis, type 1 2019-11-04 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 1359 of the NF1 protein (p.Pro1359Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. This variant is reported as two separate single-nucleotide changes in population databases (c.4074C>A, ExAC 0.0008% and c.4075C>A, ExAC 0.0008%). However, in the read data for the individual displayed in the ExAC browser, these two variants are in cis. This recapitulates the variant observed here (c.4074_4075delCCinsAA) and indicates that this variant is very likely present in the population databases at 0.0008%. It has not been reported in the literature in individuals with 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, 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.
Ambry Genetics RCV000574174 SCV000663110 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-28 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (benign)

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