ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3611G>T (p.Arg1204Leu)

dbSNP: rs1057521848
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000425910 SCV000524765 pathogenic not provided 2022-12-28 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect: impaired interaction with SPRED1 (Hirata et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); 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: 25486365, 22807134, 26635368)
Labcorp Genetics (formerly Invitae), Labcorp RCV002525376 SCV002948532 pathogenic Neurofibromatosis, type 1 2022-02-21 criteria provided, single submitter clinical testing This variant disrupts the p.Arg1204 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10336779, 10607834, 22807134, 27322474). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects NF1 function (PMID: 26635368). 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: 384082). This missense change has been observed in individuals with neurofibromatosis type I (PMID: 26635368). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1204 of the NF1 protein (p.Arg1204Leu). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003470384 SCV004198266 likely pathogenic Juvenile myelomonocytic leukemia 2023-10-10 criteria provided, single submitter clinical testing

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