ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.6755A>T (p.Lys2252Met) (rs1060500344)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000463991 SCV000542154 likely pathogenic Neurofibromatosis, type 1 2016-06-16 criteria provided, single submitter clinical testing This sequence change replaces lysine with methionine at codon 2252 of the NF1 protein (p.Lys2252Met). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with neurofibromatosis type 1 (NF1) (PMID: 25325900) and to segregate with the disease in a family (Invitae Database). This variant is also known as p.Lys2273Met in the literature Experimental studies performed by another diagnostic lab have shown that this missense change leads to the skipping of exon 36 during mRNA splicing. 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, this variant is a rare missense change that segregates with NF1 in one family and alters mRNA splicing. For these reasons, it has been classified as Likely Pathogenic.

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