ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1410A>C (p.Glu470Asp)

gnomAD frequency: 0.00001  dbSNP: rs786203090
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166241 SCV000217021 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-17 criteria provided, single submitter clinical testing The p.E470D variant (also known as c.1410A>C), located in coding exon 13 of the NF1 gene, results from an A to C substitution at nucleotide position 1410. The glutamic acid at codon 470 is replaced by aspartic acid, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6457 samples (12914 alleles) with coverage at this position.<span style="background-color:initial">To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 110000 alleles tested) in our clinical cohort.<span style="background-color:initial">This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis.<span style="background-color:initial">Since supporting evidence is limited at this time, the clinical significance of p.E470D remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000809613 SCV000949775 uncertain significance Neurofibromatosis, type 1 2024-03-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 470 of the NF1 protein (p.Glu470Asp). 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: 186619). 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.
Genome-Nilou Lab RCV000809613 SCV002561914 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV004558388 SCV005047525 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-07-16 criteria provided, single submitter clinical testing The c.1410A>C (p.E470D) alteration is located in exon 13 (coding exon 13) of the NF1 gene. This alteration results from a A to C substitution at nucleotide position 1410, causing the glutamic acid (E) at amino acid position 470 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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