ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1235A>G (p.Asn412Ser)

dbSNP: rs1567836090
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001220956 SCV001392971 uncertain significance Neurofibromatosis, type 1 2022-11-12 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NF1 protein function. ClinVar contains an entry for this variant (Variation ID: 949487). This missense change has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 18546366). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 412 of the NF1 protein (p.Asn412Ser).
Medical Genetics, University of Parma RCV001220956 SCV002567772 likely pathogenic Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing
GeneDx RCV002466637 SCV002762164 likely pathogenic not provided 2022-06-07 criteria provided, single submitter clinical testing Demonstrated to create a new splice site resulting in an in-frame loss of Val411_Asn420 in patient RNA (Pros et al., 2008); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 18546366)

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