ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.5974A>G (p.Ser1992Gly) (rs876658710)

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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 RCV000221400 SCV000274327 uncertain significance Hereditary cancer-predisposing syndrome 2015-03-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (benign)
GeneDx RCV000519724 SCV000620951 uncertain significance not provided 2017-09-19 criteria provided, single submitter clinical testing The S1992G variant in the NF1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Since Serine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. In addition, this substitution occurs at a position that is conserved across species, and in silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, we consider S1992G to be a variant of uncertain significance.
Invitae RCV000800106 SCV000939806 uncertain significance Neurofibromatosis, type 1 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces serine with glycine at codon 1992 of the NF1 protein (p.Ser1992Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 230689). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or 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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