ClinVar Miner

Submissions for variant NM_000435.3(NOTCH3):c.1463T>G (p.Val488Gly)

gnomAD frequency: 0.00001  dbSNP: rs760245739
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001923587 SCV002190053 uncertain significance not provided 2022-07-06 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 488 of the NOTCH3 protein (p.Val488Gly). This variant is present in population databases (rs760245739, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with NOTCH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1420792). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Revvity Omics, Revvity RCV001923587 SCV003816034 uncertain significance not provided 2022-11-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV003289234 SCV003956426 uncertain significance Inborn genetic diseases 2023-04-24 criteria provided, single submitter clinical testing The c.1463T>G (p.V488G) alteration is located in exon 9 (coding exon 9) of the NOTCH3 gene. This alteration results from a T to G substitution at nucleotide position 1463, causing the valine (V) at amino acid position 488 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic RCV001923587 SCV005408765 uncertain significance not provided 2023-10-30 criteria provided, single submitter clinical testing 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.