ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.274A>G (p.Lys92Glu)

dbSNP: rs1555605396
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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 RCV002317247 SCV000670524 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2023-08-04 criteria provided, single submitter clinical testing The p.K92E variant (also known as c.274A>G), located in coding exon 3 of the NF1 gene, results from an A to G substitution at nucleotide position 274. The lysine at codon 92 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000704437 SCV000833386 uncertain significance Neurofibromatosis, type 1 2024-04-17 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 92 of the NF1 protein (p.Lys92Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 484087). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function with a positive predictive value of 95%. 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.
Genome-Nilou Lab RCV000704437 SCV002561431 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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