ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.947T>G (p.Leu316Trp)

gnomAD frequency: 0.00005  dbSNP: rs750633919
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000436646 SCV000520003 uncertain significance not provided 2022-10-26 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16324214, 16532029, 11756419, 16983642, 17134719, 22482125)
Invitae RCV000534581 SCV000628888 uncertain significance Neurofibromatosis, type 2 2024-02-01 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 316 of the NF2 protein (p.Leu316Trp). This variant is present in population databases (rs750633919, gnomAD 0.01%). This missense change has been observed in individual(s) with bilateral vestibular schwannomas or breast cancer (PMID: 16983642, 35264596). ClinVar contains an entry for this variant (Variation ID: 380975). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NF2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect NF2 function (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.
Ambry Genetics RCV000561700 SCV000674139 benign Hereditary cancer-predisposing syndrome 2021-08-06 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Mendelics RCV000534581 SCV000839517 uncertain significance Neurofibromatosis, type 2 2018-07-02 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000534581 SCV002044866 uncertain significance Neurofibromatosis, type 2 2021-11-07 criteria provided, single submitter clinical testing

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