ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.1972C>T (p.Leu658Phe) (rs763901597)

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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 RCV000220178 SCV000275512 uncertain significance Hereditary cancer-predisposing syndrome 2015-05-04 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 RCV000466869 SCV000542203 uncertain significance Neurofibromatosis, type 1 2018-12-31 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 658 of the NF1 protein (p.Leu658Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs763901597, ExAC 0.003%). This variant has been reported in an individual in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 231610). 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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