ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1004A>G (p.Asn335Ser)

gnomAD frequency: 0.00001  dbSNP: rs758212945
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558546 SCV000628340 uncertain significance Neurofibromatosis, type 1 2023-10-26 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 335 of the NF1 protein (p.Asn335Ser). This variant is present in population databases (rs758212945, gnomAD 0.007%). 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: 457510). 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 not expected to disrupt NF1 protein function with a negative 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 RCV002316482 SCV000666807 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-12-23 criteria provided, single submitter clinical testing The p.N335S variant (also known as c.1004A>G), located in coding exon 9 of the NF1 gene, results from an A to G substitution at nucleotide position 1004. The asparagine at codon 335 is replaced by serine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000558546 SCV002561856 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Medical Genetics, University of Parma RCV000558546 SCV002567763 uncertain significance Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing

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