ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.5788T>C (p.Cys1930Arg)

dbSNP: rs2069454402
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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 RCV001247733 SCV001421173 pathogenic Neurofibromatosis, type 1 2024-12-24 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1909 of the NF1 protein (p.Cys1909Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurofibromatosis type I and moyamoya syndrome (PMID: 16835897, 28422438; internal data). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 971853). 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%. Experimental studies have shown that this missense change does not substantially affect NF1 function (PMID: 22105171). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001565195 SCV001788496 likely pathogenic not provided 2023-11-08 criteria provided, single submitter clinical testing Published functional studies are inconclusive; variant does not affect LRD domain protein-interaction, but affects dendritic spinogenesis in vitro (PMID: 22105171); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28422438, 16835897, 22105171, 36980803)
Genome-Nilou Lab RCV001247733 SCV002560147 likely pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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