ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.1745G>A (p.Cys582Tyr) (rs104893690)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000477640 SCV000550987 pathogenic Familial hypocalciuric hypercalcemia; Hypocalcemia, autosomal dominant 1 2019-11-28 criteria provided, single submitter clinical testing 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. This variant is not present in population databases (rs104893690, ExAC no frequency). 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). 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. 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. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000008819 SCV000029029 pathogenic Neonatal severe hyperparathyroidism 1995-12-01 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.