ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2288T>G (p.Leu763Arg) (rs199474762)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000196515 SCV000254486 pathogenic Neurofibromatosis, type 1 2019-12-10 criteria provided, single submitter clinical testing This sequence change replaces leucine with arginine at codon 763 of the NF1 protein (p.Leu763Arg). The leucine residue is moderately 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 in an individual(s) with clinical features of neurofibromatosis type 1 (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 216396). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Leu763 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10712197, 16005615, 21354044, 21520333). 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.
Ambry Genetics RCV000222376 SCV000274651 likely pathogenic Hereditary cancer-predisposing syndrome 2015-03-27 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Well-characterized mutation at same position;Other strong data supporting pathogenic classification;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000196515 SCV000781944 likely pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing

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