ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3706T>C (p.Trp1236Arg)

dbSNP: rs1555615111
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522650 SCV000619355 likely pathogenic not provided 2017-07-24 criteria provided, single submitter clinical testing The W1236R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). W1236R is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within the GTPase activating protein kinase domain that is conserved across species; this domain has been shown to be critical for NF1 protein function (Thomas et al., 2012). In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Medical Genetics, University of Parma RCV002279317 SCV002567785 likely pathogenic Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV002358412 SCV002625221 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2020-10-30 criteria provided, single submitter clinical testing The p.W1236R variant (also known as c.3706T>C), located in coding exon 27 of the NF1 gene, results from a T to C substitution at nucleotide position 3706. The tryptophan at codon 1236 is replaced by arginine, an amino acid with dissimilar properties. 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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