ClinVar Miner

Submissions for variant NM_002880.4(RAF1):c.332G>A (p.Arg111His)

dbSNP: rs996417348
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001196473 SCV001367081 uncertain significance LEOPARD syndrome 2 2020-01-26 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PM2,PP3.
Labcorp Genetics (formerly Invitae), Labcorp RCV001859185 SCV002230446 uncertain significance RASopathy 2024-08-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 111 of the RAF1 protein (p.Arg111His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 930654). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RAF1 protein function. 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.
Ambry Genetics RCV002320427 SCV002611268 uncertain significance Cardiovascular phenotype 2022-04-04 criteria provided, single submitter clinical testing The p.R111H variant (also known as c.332G>A), located in coding exon 3 of the RAF1 gene, results from a G to A substitution at nucleotide position 332. The arginine at codon 111 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well 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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