Submissions for variant NM_000268.4(NF2):c.161T>G (p.Leu54Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002401053	SCV002707369	uncertain significance	Hereditary cancer-predisposing syndrome	2020-06-22	criteria provided, single submitter	clinical testing	The p.L54R variant (also known as c.161T>G), located in coding exon 2 of the NF2 gene, results from a T to G substitution at nucleotide position 161. The leucine at codon 54 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health	RCV004007342	SCV004830923	uncertain significance	Neurofibromatosis, type 2	2023-06-26	criteria provided, single submitter	clinical testing	This missense variant replaces leucine with arginine at codon 54 of the NF2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with NF2-related disorders in the literature. This variant has been identified in 1/251494 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.