ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.3722G>A (p.Arg1241Gln) (rs543387071)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166937 SCV000217756 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-08 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Invitae RCV000204384 SCV000261776 uncertain significance Neurofibromatosis, type 1 2019-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1241 of the NF1 protein (p.Arg1241Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with neurofibromatosis type 1 (PMID: 25074460). ClinVar contains an entry for this variant (Variation ID: 187226). 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.
GeneDx RCV000680821 SCV000808268 uncertain significance not provided 2018-08-31 criteria provided, single submitter clinical testing This variant is denoted NF1 c.3722G>A at the cDNA level, p.Arg1241Gln (R1241Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant was observed in an individual with neurofibromatosis type 1 (Pasmant 2015). NF1 Arg1241Gln was observed at an allele frequency of 0.007% (1/15,002) in individuals of European (Non-Finnish) ancestry in large population cohorts (Lek 2016). This variant is located in the GTPase activating protein domain (Thomas 2012). In-silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether NF1 Arg1241Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Gharavi Laboratory,Columbia University RCV000680821 SCV000920692 uncertain significance not provided 2018-09-16 no assertion criteria provided research

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