Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV003108240 | SCV003761552 | pathogenic | Pseudohypoparathyroidism type I A | 2023-01-25 | criteria provided, single submitter | clinical testing | reclassification due to de novo occurrence confirmed by segregation analysis |
Labcorp Genetics |
RCV005099230 | SCV005741914 | uncertain significance | not provided | 2024-02-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 160 of the GNAS protein (p.Arg160Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of pseudohypoparathyroidism (Invitae). ClinVar contains an entry for this variant (Variation ID: 2412807). 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 not expected to disrupt GNAS protein function with a negative predictive value of 80%. 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. |