ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1135T>C (p.Cys379Arg)

dbSNP: rs1060500281
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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 RCV000463618 SCV000542045 pathogenic Neurofibromatosis, type 1 2024-04-24 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 379 of the NF1 protein (p.Cys379Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of neurofibromatosis, type 1 (PMID: 31573083; Invitae). ClinVar contains an entry for this variant (Variation ID: 404470). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV003226927 SCV003923371 likely pathogenic not provided 2023-06-29 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect: impaired ability to inhibit GTP-Ras activity and reduced NF1 expression (Long et al., 2022); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31573083, 34694046)

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