ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1244A>G (p.His415Arg)

dbSNP: rs1555611097
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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 RCV000574709 SCV000674070 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-07 criteria provided, single submitter clinical testing The p.H415R variant (also known as c.1244A>G), located in coding exon 11 of the NF1 gene, results from an A to G substitution at nucleotide position 1244. The histidine at codon 415 is replaced by arginine, 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 6497 samples (12994 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 110000alleles tested) in our clinical cohort.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 alterationremains unclear.
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000659981 SCV000781897 uncertain significance Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000659981 SCV000938076 uncertain significance Neurofibromatosis, type 1 2023-10-22 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 415 of the NF1 protein (p.His415Arg). 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: 485935). 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. 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 RCV000659981 SCV002561881 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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