ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.6801A>G (p.Gln2267=) (rs1064794756)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487177 SCV000569886 likely pathogenic not provided 2018-01-24 criteria provided, single submitter clinical testing This variant is denoted NF1 c.6801A>G at the DNA level. This variant is silent at the coding level, preserving a Glutamine at codon 2267. Although multiple splicing models do not predict this variant to cause abnormal splicing, Hernandez-Imaz et al. (2013) suggest that NF1 c.6801A>G causes skipping of exon 37. In addition, Baralle et al. (2006) report the presence of an exon splicing enhancer (ESE) near this variant with changes in the ESE causing exon 37 skipping. However, in the absence of RNA or functional studies corroborating that NF1 c.6801A>G leads to skipping of exon 37, the actual effect of this variant is unknown. This variant has been observed in at least one individual with features suggestive of Neurofibromatosis Type 1 (Valero 2011). NF1 c.6801A>G was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The nucleotide which is altered, an adenine (A) at base 6801, is conserved in mammals. Based on currently available information, it is unclear whether NF1 c.6801A>G is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000546979 SCV000628737 pathogenic Neurofibromatosis, type 1 2017-09-19 criteria provided, single submitter clinical testing This sequence change affects codon 2267 of the NF1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NF1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Neurofibromatosis type 1 (NF1) in the literature (PMID: 21354044) and in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 420870). It has been suggested that this variant results in skipping of exon 37, but functional studies have not been published in the literature (PMID: 21354044, 22925204). For these reasons, this variant has been classified as Pathogenic.

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