ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.5509G>A (p.Asp1837Asn)

gnomAD frequency: 0.00001  dbSNP: rs771597781
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000218141 SCV000272220 uncertain significance not specified 2015-12-16 criteria provided, single submitter clinical testing The p.Asp1837Asn variant in NF1 has not been previously reported in individuals with a RASopathy disorder, but has been identified in 2/66726 European chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs771597781). Computational prediction tools and conservation analysis do no t provide strong support for or against an impact to the protein. In summary, th e clinical significance of the p.Asp1837Asn variant is uncertain.
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000660078 SCV000782052 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002319464 SCV001186080 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2019-08-22 criteria provided, single submitter clinical testing The p.D1816N variant (also known as c.5446G>A), located in coding exon 37 of the NF1 gene, results from a G to A substitution at nucleotide position 5446. The aspartic acid at codon 1816 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000660078 SCV002263270 uncertain significance Neurofibromatosis, type 1 2023-09-10 criteria provided, single submitter clinical testing 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. 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. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1816 of the NF1 protein (p.Asp1816Asn). ClinVar contains an entry for this variant (Variation ID: 229063). This variant is also known as c.5509G>A. This missense change has been observed in individual(s) with suspected RASopathy (PMID: 32107864). This variant is present in population databases (rs771597781, gnomAD 0.003%).

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