ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4243A>C (p.Asn1415His)

dbSNP: rs1555618518
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Total submissions: 4
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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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000627054 SCV000939681 pathogenic Neurofibromatosis, type 1 2022-11-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function. ClinVar contains an entry for this variant (Variation ID: 523625). This missense change has been observed in individual(s) with neurofibromatosis, type 1 (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 1394 of the NF1 protein (p.Asn1394His).
GeneDx RCV000756433 SCV001831822 likely pathogenic not provided 2021-10-18 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31717729, 22807134, 25486365)

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