ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4180A>C (p.Asn1394His) (rs1555618518)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000627054 SCV000747761 uncertain significance Neurofibromatosis, type 1 2017-11-23 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756433 SCV000884251 uncertain significance not provided 2018-02-23 criteria provided, single submitter clinical testing The NF1 c.4243A>C; p.Asn1415His variant, also known as c.4180A>C; p.Asn1394His for NM000267.3, to our knowledge, is not reported in the medical literature or in gene-specific databases. This variant is also absent from the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The asparagine at codon 1415 is highly conserved and computational algorithms (Alamut v.2.10) predict this variant to be deleterious. However, due to lack of clinical and functional data, the clinical significance of this variant cannot be determined with certainty.
Invitae RCV000627054 SCV000939681 likely pathogenic Neurofibromatosis, type 1 2019-07-31 criteria provided, single submitter clinical testing This sequence change replaces asparagine with histidine at codon 1394 of the NF1 protein (p.Asn1394His). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with neurofibromatosis, type 1 (Invitae). ClinVar contains an entry for this variant (Variation ID: 523625). 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: "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.

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