ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1018G>A (p.Ala340Thr) (rs780430071)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000632653 SCV000753839 uncertain significance Neurofibromatosis, type 2 2020-10-09 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 340 of the NF2 protein (p.Ala340Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs780430071, ExAC 0.02%). This variant has not been reported in the literature in individuals with NF2-related disease. 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. 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 RCV001009686 SCV001169784 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-08 criteria provided, single submitter clinical testing The p.A340T variant (also known as c.1018G>A), located in coding exon 11 of the NF2 gene, results from a G to A substitution at nucleotide position 1018. The alanine at codon 340 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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