ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3578T>C (p.Phe1193Ser)

dbSNP: rs199474780
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000497226 SCV003461813 pathogenic Neurofibromatosis, type 1 2022-05-14 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1193 of the NF1 protein (p.Phe1193Ser). This missense change has been observed in individual(s) with neurofibromatosis type I (PMID: 28961165). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 431623). 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. This variant disrupts the p.Phe1193Cys amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11735023). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Medical Genetics, University of Parma RCV000497226 SCV000588763 uncertain significance Neurofibromatosis, type 1 2017-02-02 no assertion criteria provided clinical testing

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