ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3437T>A (p.Val1146Asp)

dbSNP: rs2067137147
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001227859 SCV001400237 uncertain significance Neurofibromatosis, type 1 2019-08-20 criteria provided, single submitter clinical testing This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with aspartic acid at codon 1146 of the NF1 protein (p.Val1146Asp). The valine residue is moderately conserved and there is a large physicochemical difference between valine and aspartic acid. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV001776154 SCV002012786 likely pathogenic not provided 2023-09-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: Martorana2022[CaseReport], 22807134, 2121369, 25486365)
Genome-Nilou Lab RCV001227859 SCV002560296 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Medical Genetics, University of Parma RCV001227859 SCV002567775 likely pathogenic Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001776154 SCV005624571 uncertain significance not provided 2024-05-13 criteria provided, single submitter clinical testing The NF1 c.3437T>A (p.Val1146Asp) variant has not been reported in individuals with NF1-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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