ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2850G>C (p.Gln950His) (rs863224446)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000198059 SCV000253691 likely pathogenic Neurofibromatosis, type 1 2015-03-30 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 950 of the NF1 protein (p.Gln950His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. It also falls at the last nucleotide of exon 21 of the NF1 mRNA. This variant has not been published in the literature and is not present in population databases. Nucleotide substitutions at the last nucleotide of the exon are relatively common causes of aberrant splicing (PMID: 17576681). Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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, this is a novel sequence change that is predicted to disrupt mRNA splicing. Furthermore, the phenotype and family history of this patient is consistent with a pathogenic NF1 mutation. For these reasons, this variant has been classified as Likely Pathogenic.

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