ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4372G>A (p.Glu1458Lys)

dbSNP: rs1135402858
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Medical Genetics, University of Parma RCV000497096 SCV000588781 pathogenic Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing
Invitae RCV000497096 SCV002185903 pathogenic Neurofibromatosis, type 1 2023-05-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Glu1437 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1437 of the NF1 protein (p.Glu1437Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 28961165). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 431639). 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.

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