ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.713C>T (p.Ala238Val) (rs761195572)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701250 SCV000830041 uncertain significance Neurofibromatosis, type 2 2020-09-03 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 238 of the NF2 protein (p.Ala238Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). 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 do not agree on the potential impact of this missense change (SIFT: Deleterious; 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.
Ambry Genetics RCV001026080 SCV001188391 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-10 criteria provided, single submitter clinical testing The p.A238V variant (also known as c.713C>T), located in coding exon 8 of the NF2 gene, results from a C to T substitution at nucleotide position 713. The alanine at codon 238 is replaced by valine, an amino acid with similar properties. This alteration has been reported in an individual with hepatocellular carcinoma (Yoo NJ et al. Pathology, 2012 Jan;44:29-32). 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.

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