ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1012C>T (p.Arg338Cys) (rs761795291)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000432645 SCV000536556 uncertain significance not provided 2020-07-20 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28481359, 18547414)
Invitae RCV000559539 SCV000628841 uncertain significance Neurofibromatosis, type 2 2019-11-02 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 338 of the NF2 protein (p.Arg338Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. The frequency data for this variant (rs761795291) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a NF2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001016950 SCV001177960 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-17 criteria provided, single submitter clinical testing The p.R338C variant (also known as c.1012C>T), located in coding exon 11 of the NF2 gene, results from a C to T substitution at nucleotide position 1012. The arginine at codon 338 is replaced by cysteine, an amino acid with highly dissimilar 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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