ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2339C>G (p.Thr780Arg) (rs199474746)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000553902 SCV000628434 likely pathogenic Neurofibromatosis, type 1 2019-08-19 criteria provided, single submitter clinical testing This sequence change replaces threonine with arginine at codon 780 of the NF1 protein (p.Thr780Arg). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with neurofibromatosis type 1 (PMID: 16786508, 16944272, Invitae). ClinVar contains an entry for this variant (Variation ID: 457581). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Thr780 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10712197, 12552569, 11735023, 26478990, 16944272, 15146469, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000553902 SCV000781949 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Gharavi Laboratory,Columbia University RCV000681848 SCV000809326 likely pathogenic not provided 2018-09-16 no assertion criteria provided research

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