ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4168C>G (p.Leu1390Val) (rs199474789)

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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,Center for Human Genetics, Inc RCV000660051 SCV000782011 likely pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000660051 SCV001234754 pathogenic Neurofibromatosis, type 1 2019-03-21 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 1390 of the NF1 protein (p.Leu1390Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual with clinical features consistent with NF1-Noonan syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 547642). 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.Leu1390 amino acid residue in NF1. Other variant(s) that disrupt this residue have been observed in individuals with NF1-related conditions (PMID: 19845691), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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