ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.2851G>T (p.Val951Phe)

dbSNP: rs1597716277
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Medical Genetics, University of Parma RCV002279170 SCV002567773 likely pathogenic Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing
Invitae RCV002279170 SCV003441774 pathogenic Neurofibromatosis, type 1 2022-05-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 951 of the NF1 protein (p.Val951Phe). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of neurofibromatosis type 1 (PMID: 25074460, 26478990, 31370276, 31717729). 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"). Studies have shown that this missense change results in skipping of exon 22 and introduces a premature termination codon (PMID: 26478990). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.

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