ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.5642C>T (p.Ala1881Val) (rs1465309384)

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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 RCV000562235 SCV000670513 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000681199 SCV000808658 uncertain significance not provided 2018-04-06 criteria provided, single submitter clinical testing This variant is denoted NF1 c.5642C>T at the cDNA level, p.Ala1881Val (A1881V) at the protein level, and results in the change of an Alanine to a Valine (GCC>GTC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 Ala1881Val was not observed in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether NF1 Ala1881Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000632437 SCV000753618 uncertain significance Neurofibromatosis, type 1 2018-10-24 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 1881 of the NF1 protein (p.Ala1881Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine 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 disease. ClinVar contains an entry for this variant (Variation ID: 484077). 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: "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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