ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.3103C>T (p.Pro1035Ser)

gnomAD frequency: 0.00001  dbSNP: rs762383457
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 RCV000697929 SCV000826563 uncertain significance Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1035 of the CASR protein (p.Pro1035Ser). This variant is present in population databases (rs762383457, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CASR-related conditions. ClinVar contains an entry for this variant (Variation ID: 575649). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV002386223 SCV001179914 uncertain significance Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis 2021-11-10 criteria provided, single submitter clinical testing The p.P1035S variant (also known as c.3103C>T), located in coding exon 6 of the CASR gene, results from a C to T substitution at nucleotide position 3103. The proline at codon 1035 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.