Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Undiagnosed Diseases Network, |
RCV000017323 | SCV000926990 | likely pathogenic | Pseudohypoparathyroidism | 2019-01-29 | criteria provided, single submitter | clinical testing | |
Gene |
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 |