ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.8120C>T (p.Ala2707Val) (rs760973918)

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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 RCV000215349 SCV000273939 uncertain significance Hereditary cancer-predisposing syndrome 2015-02-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes)
GeneDx RCV000681173 SCV000808631 uncertain significance not provided 2018-03-19 criteria provided, single submitter clinical testing This variant is denoted NF1 c.8120C>T at the cDNA level, p.Ala2707Val (A2707V) at the protein level, and results in the change of an Alanine to a Valine (GCT>GTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 Ala2707Val was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the C-terminal domain (Luo 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether NF1 Ala2707Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000698786 SCV000827472 uncertain significance Neurofibromatosis, type 1 2018-03-29 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 2707 of the NF1 protein (p.Ala2707Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs760973918, ExAC 0.01%). This variant has not been reported in the literature in individuals with NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 230400). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; 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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