ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.169C>T (p.Arg57Ter) (rs121434259)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255708 SCV000322362 pathogenic not provided 2016-07-18 criteria provided, single submitter clinical testing R57X in the NF2 gene is a recurrent pathogenic variant that has been reported numerous times in association withNF2 (Rouleau et al., 1993; Evans et al., 1998; Kluwe et al., 2000; Sestini et al., 2008; Baumer et al., 2013). Thisvariant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediatedmRNA decay. The R57X variant was not observed in approximately 6500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in thesepopulations. We interpret R57X as a pathogenic variant.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000660130 SCV000782121 pathogenic Neurofibromatosis, type 2 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000660130 SCV000945759 pathogenic Neurofibromatosis, type 2 2020-07-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg57*) 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 observed in several individuals affected with neurofibromatosis type 2 (PMID: 8882871, 8379998, 26073919, 18033041, 9884492). ClinVar contains an entry for this variant (Variation ID: 3285). Loss-of-function variants in NF2 are known to be pathogenic (PMID: 9643284, 16983642). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000660130 SCV001362183 pathogenic Neurofibromatosis, type 2 2019-08-13 criteria provided, single submitter clinical testing Variant summary: NF2 c.169C>T (p.Arg57X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251490 control chromosomes. c.169C>T has been reported in the literature in multiple individuals affected with Neurofibromatosis Type 2 (Rouleau_1993, Kluwe_1996, Evans_1998, Goutagny_2012) . 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 clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar (after 2014) and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000003446 SCV000023604 pathogenic Meningioma 1995-03-01 no assertion criteria provided literature only
Human Genetics - Radboudumc,Radboudumc RCV000255708 SCV001957450 pathogenic not provided no assertion criteria provided clinical testing

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