ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.3446T>C (p.Met1149Thr)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000818100 SCV000958695 uncertain significance Neurofibromatosis, type 1 2018-08-23 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 1149 of the NF1 protein (p.Met1149Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a NF1-related disease. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). Variants that disrupt the p.Met1149 amino acid residue in NF1 have been observed in affected individuals (PMID: 23656349, 24711935, 28706617, 16944272, 27322474, Invitae). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Medical Genomics Laboratory,Department of Genetics UAB RCV000818100 SCV000999178 pathogenic Neurofibromatosis, type 1 2019-06-05 criteria provided, single submitter clinical testing

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