Submissions for variant NM_001042492.3(NF1):c.4109A>C (p.Gln1370Pro)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002319012	SCV001183552	uncertain significance	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2022-03-30	criteria provided, single submitter	clinical testing	The p.Q1370P variant (also known as c.4109A>C), located in coding exon 30 of the NF1 gene, results from an A to C substitution at nucleotide position 4109. The glutamine at codon 1370 is replaced by proline, an amino acid with similar properties. This variant has been reported in an individual with a clinical suspicion of neurofibromatosis type 1 (NF1) (Bonatti F et al. Int J Mol Sci, 2017 Sep;18:). 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.
Invitae	RCV000497125	SCV001391591	uncertain significance	Neurofibromatosis, type 1	2019-07-26	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in an individual with clinical features of neurofibromatosis type 1 (PMID: 28961165). ClinVar contains an entry for this variant (Variation ID: 431633). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with proline at codon 1370 of the NF1 protein (p.Gln1370Pro). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine and proline.
Genome-Nilou Lab	RCV000497125	SCV002560381	uncertain significance	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Medical Genetics, University of Parma	RCV000497125	SCV000588773	uncertain significance	Neurofibromatosis, type 1	2017-02-02	no assertion criteria provided	clinical testing

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