ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1271G>A (p.Arg424His) (rs751182657)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000997900 SCV001153661 uncertain significance not provided 2017-04-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV001010660 SCV001170892 uncertain significance Hereditary cancer-predisposing syndrome 2020-07-06 criteria provided, single submitter clinical testing The p.R424H variant (also known as c.1271G>A), located in coding exon 12 of the NF2 gene, results from a G to A substitution at nucleotide position 1271. The arginine at codon 424 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly 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.
Invitae RCV001218134 SCV001390006 uncertain significance Neurofibromatosis, type 2 2020-07-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 424 of the NF2 protein (p.Arg424His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs751182657, ExAC 0.007%). This variant has not been reported in the literature in individuals with NF2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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.

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