ClinVar Miner

Submissions for variant NM_005343.4(HRAS):c.11A>C (p.Tyr4Ser)

dbSNP: rs764622691
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001912723 SCV002171062 uncertain significance Costello syndrome 2021-01-17 criteria provided, single submitter clinical testing 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 HRAS protein function. This sequence change replaces tyrosine with serine at codon 4 of the HRAS protein (p.Tyr4Ser). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with HRAS-related conditions. 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.
Clinical Genomics Laboratory, Stanford Medicine RCV001912723 SCV005901568 uncertain significance Costello syndrome 2023-06-05 criteria provided, single submitter clinical testing The p.Tyr4Ser variant in the HRAS gene has not been previously reported in association with disease.This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). This variant is present in ClinVar (Variation ID: 1398020). The tyrosine at position 4 is evolutionarily conserved. Computational tools predict that the p.Tyr4Ser variant is deleterious; however, the accuracy of in silico algorithms is limited.These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Tyr4Ser variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PM2; PP3]

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.