ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.6788C>T (p.Thr2263Ile) (rs747881072)

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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 RCV000575993 SCV000663159 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000632303 SCV000753479 uncertain significance Neurofibromatosis, type 1 2018-07-11 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 2263 of the NF1 protein (p.Thr2263Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 480135). 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 and their clinical significance is uncertain. 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.

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