ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3586C>G (p.Leu1196Val)

dbSNP: rs1555615039
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000660038 SCV000781990 likely pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000660038 SCV000958325 pathogenic Neurofibromatosis, type 1 2024-12-24 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1196 of the NF1 protein (p.Leu1196Val). 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: 26740943; internal data). ClinVar contains an entry for this variant (Variation ID: 547629). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NF1 protein function. This variant disrupts the p.Leu1196 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23047742, 31776437; internal data). 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.
GeneDx RCV003163040 SCV003915398 likely pathogenic not provided 2022-10-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in a cohort of individuals with clinical characteristics of neurofibromatosis type 1 (Bianchessi et al., 2015); This variant is associated with the following publications: (PMID: 25486365, 22807134, 2121369, 26740943)

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