ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4460C>T (p.Pro1487Leu)

gnomAD frequency: 0.00001  dbSNP: rs2067663223
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001290951 SCV001479283 uncertain significance Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001290951 SCV002180725 uncertain significance Neurofibromatosis, type 1 2022-03-08 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 996533). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1466 of the NF1 protein (p.Pro1466Leu).
Genome-Nilou Lab RCV001290951 SCV002560430 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002327630 SCV002629880 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2019-09-03 criteria provided, single submitter clinical testing The p.P1466L variant (also known as c.4397C>T), located in coding exon 33 of the NF1 gene, results from a C to T substitution at nucleotide position 4397. The proline at codon 1466 is replaced by leucine, an amino acid with 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.

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