ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.401C>T (p.Pro134Leu)

dbSNP: rs1029716358
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000524823 SCV000628870 uncertain significance Neurofibromatosis, type 2 2017-07-25 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 134 of the NF2 protein (p.Pro134Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NF2-related disease. This variant is not present in population databases (ExAC no frequency).
Mendelics RCV000524823 SCV000839513 uncertain significance Neurofibromatosis, type 2 2018-07-02 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000524823 SCV002044846 uncertain significance Neurofibromatosis, type 2 2021-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002358459 SCV002619650 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-12 criteria provided, single submitter clinical testing The p.P134L variant (also known as c.401C>T), located in coding exon 4 of the NF2 gene, results from a C to T substitution at nucleotide position 401. The proline at codon 134 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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