ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.667T>C (p.Trp223Arg)

dbSNP: rs1555608740
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000659966 SCV000781878 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
GeneDx RCV000680812 SCV000808258 likely pathogenic not provided 2020-06-17 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: 24803665, 29566708, 25541118, 16944272, 27838393, 31370276)
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000659966 SCV001479108 pathogenic Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000659966 SCV002231849 pathogenic Neurofibromatosis, type 1 2024-12-18 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 223 of the NF1 protein (p.Trp223Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 16944272, 25541118, 29566708). ClinVar contains an entry for this variant (Variation ID: 547570). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt NF1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000659966 SCV002561594 likely pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Medical Genetics, University of Parma RCV000659966 SCV002567803 likely pathogenic Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV000659966 SCV002579698 likely pathogenic Neurofibromatosis, type 1 2021-12-07 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000680812 SCV004009768 pathogenic not provided 2023-05-01 criteria provided, single submitter clinical testing NF1: PS1, PM2, PM6, PP3, PP4

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