ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.3790G>A (p.Glu1264Lys) (rs863224660)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000196980 SCV000254498 likely pathogenic Neurofibromatosis, type 1 2020-01-07 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1264 of the NF1 protein (p.Glu1264Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of neurofibromatosis type 1 (Invitae, external communication). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 216402). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV000492615 SCV000581279 pathogenic Hereditary cancer-predisposing syndrome 2015-10-12 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family

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