ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.7146C>G (p.Phe2382Leu)

dbSNP: rs2151565177
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002047430 SCV002109298 pathogenic Neurofibromatosis, type 1 2022-07-01 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2361 of the NF1 protein (p.Phe2361Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 23812910, 31717729). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1352215). 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. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV003164047 SCV003861721 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2023-03-03 criteria provided, single submitter clinical testing The p.F2361L variant (also known as c.7083C>G), located in coding exon 47 of the NF1 gene, results from a C to G substitution at nucleotide position 7083. The phenylalanine at codon 2361 is replaced by leucine, an amino acid with highly similar properties. This alteration was identified in two individuals with features of neurofibromatosis type 1 with at least one of these cases determined to be the result of a de novo mutation (Burkitt Wright EM et al. J Med Genet, 2013 Sep;50:606-13; Yao R et al. Genes (Basel), 2019 Oct;10:). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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