ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.3947A>G (p.His1316Arg) (rs751023085)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000632489 SCV000753674 uncertain significance Neurofibromatosis, type 1 2018-12-22 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 1316 of the NF1 protein (p.His1316Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. 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. 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: "Benign"; 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.
GeneDx RCV000681105 SCV000808561 uncertain significance not provided 2018-02-05 criteria provided, single submitter clinical testing This variant is denoted NF1 c.3947A>G at the cDNA level, p.His1316Arg (H1316R) at the protein level, and results in the change of a Histidine to an Arginine (CAT>CGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 His1316Arg was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the GTPase activating protein domain (Thomas 2012, 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 His1316Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV001021492 SCV001183117 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-19 criteria provided, single submitter clinical testing Insufficient evidence

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