ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.8416G>A (p.Ala2806Thr) (rs199878086)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000468064 SCV000542123 uncertain significance Neurofibromatosis, type 1 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 2806 of the NF1 protein (p.Ala2806Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs199878086, ExAC 0.02%). This variant has not been reported in the literature in individuals with NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 404536). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV000560959 SCV000662754 uncertain significance Hereditary cancer-predisposing syndrome 2015-10-07 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (benign);Rarity in general population databases (dbsnp, esp, 1000 genomes)
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825205 SCV000966482 likely benign not specified 2018-07-18 criteria provided, single submitter clinical testing The p.Ala2827Thr variant in NF1 is classified as likely benign due to a lack of conservation across species. Several species, including 8 mammals, have threonin e (Thr) at this position. It has been identified in 3/17242 East Asian chromosom es by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs199878086). ACMG/AMP Criteria applied: BP4_Strong.

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