ClinVar Miner

Submissions for variant NM_002880.4(RAF1):c.1685G>T (p.Gly562Val)

gnomAD frequency: 0.00001  dbSNP: rs746937683
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000681431 SCV000808894 uncertain significance not provided 2018-08-21 criteria provided, single submitter clinical testing The G562V variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 2/15304 (0.01%) alleles from individuals of African ancestry in large population cohorts (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, the G562V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additional evidence is needed to clarify pathogenicity, including observation in a significant number of affected individuals, segregation data, and functional evidence.
Labcorp Genetics (formerly Invitae), Labcorp RCV003768046 SCV004674669 uncertain significance RASopathy 2022-12-23 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 expected to disrupt RAF1 protein function. ClinVar contains an entry for this variant (Variation ID: 561970). This variant has not been reported in the literature in individuals affected with RAF1-related conditions. This variant is present in population databases (rs746937683, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 562 of the RAF1 protein (p.Gly562Val).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.