ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.5306G>A (p.Arg1769Gln)

dbSNP: rs1555533559
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000534787 SCV000628653 uncertain significance Neurofibromatosis, type 1 2024-08-29 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1748 of the NF1 protein (p.Arg1748Gln). 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: 457749). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Ambry Genetics RCV002316511 SCV000670586 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-08-14 criteria provided, single submitter clinical testing The p.R1748Q variant (also known as c.5243G>A), located in coding exon 37 of the NF1 gene, results from a G to A substitution at nucleotide position 5243. The arginine at codon 1748 is replaced by glutamine, an amino acid with highly 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.
Ambry Genetics RCV000622461 SCV000742170 uncertain significance Inborn genetic diseases 2017-01-23 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000534787 SCV002560535 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
GeneDx RCV003233702 SCV003930671 uncertain significance not provided 2022-12-07 criteria provided, single submitter clinical testing De novo variant with confirmed parentage in a patient referred for genetic testing at GeneDx; however, the reported clinical features are only partially consistent with the features typically observed in individuals with pathogenic variants in this gene; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published in association with an NF1-related disorder to our knowledge; This variant is associated with the following publications: (PMID: 30287823)
Fulgent Genetics, Fulgent Genetics RCV005018911 SCV005639919 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2024-06-05 criteria provided, single submitter clinical testing

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