Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000477640 | SCV000550987 | pathogenic | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2019-11-28 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Cys582 amino acid residue in CASR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17698911, 23764372). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been observed in a family and in individuals affected with familial hypocalciuric hypercalcemia (PMID: 17698911, 22192860, 23764372) and in two individuals affected with early onset hyperparathyroidism (PMID: 18219222, 8675635). ClinVar contains an entry for this variant (Variation ID: 8318). This variant is not present in population databases (rs104893690, ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 582 of the CASR protein (p.Cys582Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. For these reasons, this variant has been classified as Pathogenic. 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 CASR protein function. |
| OMIM | RCV000008819 | SCV000029029 | pathogenic | Neonatal severe primary hyperparathyroidism | 1995-12-01 | no assertion criteria provided | literature only |