ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2342A>T (p.His781Leu) (rs199474763)

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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 RCV000215892 SCV000277002 uncertain significance Hereditary cancer-predisposing syndrome 2015-07-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence,In silico models in agreement (benign),Other data supporting pathogenic classification
Invitae RCV000196521 SCV000254489 uncertain significance Neurofibromatosis, type 1 2018-08-05 criteria provided, single submitter clinical testing This sequence change replaces histidine with leucine at codon 781 of the NF1 protein (p.His781Leu). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and leucine. 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: 216398). 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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