ClinVar Miner

Submissions for variant NM_000268.3(NF2):c.947T>G (p.Leu316Trp) (rs750633919)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561700 SCV000674139 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000436646 SCV000520003 uncertain significance not provided 2018-05-23 criteria provided, single submitter clinical testing The L316W variant in the NF2 gene has been reported previously in a patient with bilateral vestibular schwannomas (Ahronowitz et al., 2007). The L316W variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L316W variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Leucine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret L316W as a variant of uncertain significance.
Invitae RCV000534581 SCV000628888 uncertain significance Neurofibromatosis, type 2 2018-08-01 criteria provided, single submitter clinical testing This sequence change replaces leucine with tryptophan at codon 316 of the NF2 protein (p.Leu316Trp). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and tryptophan. This variant is present in population databases (rs750633919, ExAC 0.02%). This variant has been reported in an individual affected with bilateral vestibular schwannomas (PMID: 16983642). ClinVar contains an entry for this variant (Variation ID: 380975). Experimental studies using a yeast two-hybrid screen have shown that this missense change does not affect the binding interaction between Merlin (the protein encoded by NF2) and HEI10 (a cell cycle regulator) (PMID: 16532029). 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.
Mendelics RCV000534581 SCV000839517 uncertain significance Neurofibromatosis, type 2 2018-07-02 criteria provided, single submitter clinical testing

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