ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.50T>C (p.Phe17Ser)

dbSNP: rs1911557433
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002337412 SCV002641938 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-02-16 criteria provided, single submitter clinical testing The p.F17S variant (also known as c.50T>C), located in coding exon 1 of the NF1 gene, results from a T to C substitution at nucleotide position 50. The phenylalanine at codon 17 is replaced by serine, an amino acid with highly dissimilar properties. This alteration was identified in a cohort of Korean patients with a confirmed or suspected clinical diagnosis of neurofibromatosis type 1 (Kang E et al. J Hum Genet, 2020 Jan;65:79-89). 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 RCV002227922 SCV003442604 likely pathogenic Neurofibromatosis, type 1 2022-11-29 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function. ClinVar contains an entry for this variant (Variation ID: 1679935). This missense change has been observed in individual(s) with neurofibromatosis, type 1 (PMID: 31776437). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 17 of the NF1 protein (p.Phe17Ser).
Hereditary Cancer Clinic, Medical College of Georgia RCV002227922 SCV002507102 likely pathogenic Neurofibromatosis, type 1 2022-05-09 no assertion criteria provided clinical testing PM2 Absent from controls. PP3 Multiple lines of computational evidence. PP4 Patient's phenotype is highly specific for a disease with a single genetic etiology. PP5 Reputable source recently reports variant as pathogenic (Variant reported in two individuals with NF1, one of whom had maternal inheritance of NF1. Kang E, Journal of Human Genetics 65:79–89. 2020)

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