ClinVar Miner

Submissions for variant NM_002880.4(RAF1):c.31A>T (p.Ile11Phe)

gnomAD frequency: 0.00001  dbSNP: rs779001930
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000761113 SCV000891029 uncertain significance Noonan syndrome 2020-09-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001207035 SCV001378372 uncertain significance RASopathy 2023-03-11 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. 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 not expected to disrupt RAF1 protein function. ClinVar contains an entry for this variant (Variation ID: 620618). This variant has not been reported in the literature in individuals affected with RAF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 11 of the RAF1 protein (p.Ile11Phe).
Ambry Genetics RCV002325461 SCV002609711 uncertain significance Cardiovascular phenotype 2020-03-02 criteria provided, single submitter clinical testing The p.I11F variant (also known as c.31A>T), located in coding exon 1 of the RAF1 gene, results from an A to T substitution at nucleotide position 31. The isoleucine at codon 11 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224387 SCV003920375 uncertain significance LEOPARD syndrome 2; Noonan syndrome 5; Dilated cardiomyopathy 1NN 2021-03-30 criteria provided, single submitter clinical testing RAF1 NM_002880.3 exon 2 p.Ile11Phe (c.31A>T): This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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