ClinVar Miner

Submissions for variant NM_000268.3(NF2):c.586C>T (p.Arg196Ter) (rs1555993336)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599281 SCV000709957 pathogenic not provided 2018-11-07 criteria provided, single submitter clinical testing The R196X nonsense variant in the NF2 gene has been reported previously in individuals diagnosed with or suspicious for neurofibromatosis type 2 (Joachim et al., 2001; Caltabiano et al., 2017). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R196X variant is not observed in large population cohorts (Lek et al., 2016). Based on currently available evidence, we consider R196X to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000554782 SCV000917898 pathogenic Neurofibromatosis, type 2 2018-07-03 criteria provided, single submitter clinical testing Variant summary: NF2 c.586C>T (p.Arg196X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 246252 control chromosomes (gnomAD). The variant, c.586C>T, has been reported in the literature in multiple individuals affected with Neurofibromatosis Type 2 (Bonne_2016, Bourn_1995, Evans_1998). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000554782 SCV000628875 pathogenic Neurofibromatosis, type 2 2018-09-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg196*) in the NF2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with neurofibromatosis type 2 (PMID: 7759081, 18033041, 8797533, 11085592). Loss-of-function variants in NF2 are known to be pathogenic (PMID: 9643284, 16983642). For these reasons, this variant has been classified as Pathogenic.

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