ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.7804C>G (p.Leu2602Val) (rs1555536721)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575517 SCV000663205 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-03 criteria provided, single submitter clinical testing In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Insufficient evidence
GeneDx RCV000681297 SCV000808759 uncertain significance not provided 2018-05-17 criteria provided, single submitter clinical testing This variant is denoted NF1 c.7804C>G at the cDNA level, p.Leu2602Val (L2602V) at the protein level, and results in the change of a Leucine to a Valine (CTA>GTA). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. NF1 Leu2602Val was not observed in large population cohorts (Lek 2016). This variant is located in C-terminal domain (Luo 2014). While protein-based in silico analysis supports that this variant does not alter protein structure/function, splicing models predict the loss of the nearby natural splice donor site. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. Based on currently available evidence, it is unclear whether NF1 Leu2602Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV001060888 SCV001225605 uncertain significance Neurofibromatosis, type 1 2019-12-11 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 2602 of the NF1 protein (p.Leu2602Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 480171). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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