ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.3921T>G (p.Ile1307Met) (rs876660805)

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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 RCV000219337 SCV000278517 uncertain significance Hereditary cancer-predisposing syndrome 2015-09-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Invitae RCV000632338 SCV000753515 uncertain significance Neurofibromatosis, type 1 2017-09-29 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 1307 of the NF1 protein (p.Ile1307Met). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 234032). 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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