ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.1496T>G (p.Leu499Arg) (rs1555612288)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc RCV000659989 SCV000781910 likely pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000659989 SCV000941482 pathogenic Neurofibromatosis, type 1 2018-10-22 criteria provided, single submitter clinical testing This sequence change replaces leucine with arginine at codon 499 of the NF1 protein (p.Leu499Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with neurofibromatosis type 1 in families and is present in an individual with suspected neurofibromatosis type 1 (PMID: 28529006, 26740943). ClinVar contains an entry for this variant (Variation ID: 547592). 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Leu499 amino acid residue in NF1. Another variant that disrupts this residue has been observed in an affected individual (Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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