ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.345A>T (p.Gln115His) (rs746369012)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000472642 SCV000553680 uncertain significance Neurofibromatosis, type 2 2020-01-13 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 115 of the NF2 protein (p.Gln115His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs746369012, ExAC 0.009%). This variant has not been reported in the literature in individuals with NF2-related disease. ClinVar contains an entry for this variant (Variation ID: 412211). 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: Tolerated; PolyPhen-2: Possibly 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 RCV001020352 SCV001181819 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-05 criteria provided, single submitter clinical testing The p.Q115H variant (also known as c.345A>T), located in coding exon 3 of the NF2 gene, results from an A to T substitution at nucleotide position 345. The glutamine at codon 115 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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