ClinVar Miner

Submissions for variant NM_000516.7(GNAS):c.344C>T (p.Pro115Leu)

dbSNP: rs137854539
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Undiagnosed Diseases Network, NIH RCV000017323 SCV000926990 likely pathogenic Pseudohypoparathyroidism 2019-01-29 criteria provided, single submitter clinical testing
GeneDx RCV002243646 SCV002513028 likely pathogenic not provided 2022-04-14 criteria provided, single submitter clinical testing Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12621129, 11600516, 16789628, 24850831, 21274345, 15070926, 31886927)
Invitae RCV002243646 SCV004298106 pathogenic not provided 2022-12-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro115 amino acid residue in GNAS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21274345, 28296742, 29059381). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 GNAS protein function. ClinVar contains an entry for this variant (Variation ID: 15953). This variant is also known as p.Pro116Leu. This missense change has been observed in individuals with pseudohypoparathyroidism type 1a (PMID: 11600516, 23884777). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 115 of the GNAS protein (p.Pro115Leu).
OMIM RCV000017322 SCV000037594 pathogenic Pseudopseudohypoparathyroidism 2001-10-01 no assertion criteria provided literature only
OMIM RCV000017323 SCV000037595 pathogenic Pseudohypoparathyroidism 2001-10-01 no assertion criteria provided literature only

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.