ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.1748A>G (p.Lys583Arg) (rs199474760)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000059158 SCV000885836 likely pathogenic not provided 2017-08-23 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc RCV000458151 SCV000781928 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000458151 SCV000542133 pathogenic Neurofibromatosis, type 1 2017-11-13 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 583 of the NF1 protein (p.Lys583Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature multiple times in individuals affected with neurofibromatosis, type 1 (PMID: 10712197, 18041031, 17726231, 16944272, 21354044, 27322474, 27074763). ClinVar contains an entry for this variant (Variation ID: 68306). Experimental studies have shown that this variant creates a cryptic splice site that removes 27 nucleotides from the mRNA transcript. This transcript was shown to escape nonsense mediated decay, but is expected to result in a disrupted protein (PMID: 18041031, 27322474). For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000059158 SCV000090687 not provided not provided no assertion provided not provided

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