ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3827G>T (p.Arg1276Leu)

dbSNP: rs137854556
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UAB Medical Genomics Laboratory, UAB Medicine RCV000856625 SCV000999184 pathogenic Neurofibromatosis, type 1 2019-06-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000856625 SCV001582128 pathogenic Neurofibromatosis, type 1 2024-09-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1276 of the NF1 protein (p.Arg1276Leu). 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: 31595648). ClinVar contains an entry for this variant (Variation ID: 694608). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt NF1 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg1276 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10712197, 15060124, 16479075, 19221814, 23668869, 27322474). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000856625 SCV002559996 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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