ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2617C>T (p.Arg873Cys) (rs199474739)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000226490 SCV000284417 uncertain significance Neurofibromatosis, type 1 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 873 of the NF1 protein (p.Arg873Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs199474739, ExAC 0.006%). This variant has been observed in individuals with neurofibromatosis type I (PMID: 15060124, 19076627, 23913538). However, in two of these individuals, pathogenic alleles were also identified in NF1, which suggests that this c.2617C>T variant was not the primary cause of disease. This variant is also known as c.2828C>T, R873T in the literature. ClinVar contains an entry for this variant (Variation ID: 68325) 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"). 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.
Ambry Genetics RCV000560998 SCV000670324 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient evidence
UniProtKB/Swiss-Prot RCV000059177 SCV000090706 not provided not provided no assertion provided not provided

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