ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2531T>G (p.Leu844Arg) (rs137854566)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000000404 SCV000829384 pathogenic Neurofibromatosis, type 1 2018-02-28 criteria provided, single submitter clinical testing This sequence change replaces leucine with arginine at codon 844 of the NF1 protein (p.Leu844Arg). 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 reported to be de novo in an individual affected with neurofibromatosis, type 1 (PMID: 15948193) and has been reported in individuals affected with neurofibromatosis, type 1 (PMID: 29290338). ClinVar contains an entry for this variant (Variation ID: 373). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Leu844Phe) has been determined to be likely pathogenic (PMID: 10980545, 15060124, 27322474). This suggests that the leucine residue is critical for NF1 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000404 SCV000020548 pathogenic Neurofibromatosis, type 1 2005-07-30 no assertion criteria provided literature only

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