ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.248A>C (p.Gln83Pro)

dbSNP: rs1060500360
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000795319 SCV000934774 pathogenic Neurofibromatosis, type 1 2023-05-25 criteria provided, single submitter clinical testing This missense change has been observed in individuals with neurofibromatosis type 1 (PMID: 23913538). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as 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: 641956). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 83 of the NF1 protein (p.Gln83Pro).
Ambry Genetics RCV002424817 SCV002742243 likely pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2019-12-20 criteria provided, single submitter clinical testing The p.Q83P variant (also known as c.248A>C), located in coding exon 3 of the NF1 gene, results from an A to C substitution at nucleotide position 248. The glutamine at codon 83 is replaced by proline, an amino acid with similar properties. This alteration was detected in an individual meeting NIH diagnostic criteria for Neurofibromatosis type 1 (NF1) (Sabbagh A et al. Hum. Mutat., 2013 Nov;34:1510-8). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
GeneDx RCV002469291 SCV002765858 likely pathogenic not provided 2022-11-10 criteria provided, single submitter clinical testing Reported to segregate with disease in individuals with neurofibromatosis type 1 from a single family in published literature, however, family-specific clinical information and pedigree were not provided (Sabbagh et al., 2013); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34418705, 23913538)

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