ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3113G>C (p.Arg1038Thr)

dbSNP: rs1060500313
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001914784 SCV002138156 pathogenic Neurofibromatosis, type 1 2021-10-02 criteria provided, single submitter clinical testing This variant disrupts a region of the NF1 protein in which other variant(s) (p.Arg1000Pro) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change results in skipping of exon 23 (also called exon 18), but is expected to preserve the integrity of the reading-frame (PMID: 18546366). This sequence change replaces arginine with threonine at codon 1038 of the NF1 protein (p.Arg1038Thr). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and threonine. RNA analysis indicates that this missense change induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 18546366). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0").

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