ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.1688T>C (p.Phe563Ser)

dbSNP: rs1553768731
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
GeneDx RCV000498666 SCV000589310 uncertain significance not provided 2017-02-01 criteria provided, single submitter clinical testing The F563S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; Exome Variant Server). F563S is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (C562Y, C565G, C568Y) have been reported in the Human Gene Mutation Database in association with CASR-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Based on the currently available information, it is unclear whether this variant is pathogenic or a rare benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV001851368 SCV002164856 uncertain significance Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 2023-05-25 criteria provided, single submitter clinical testing 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 431805). This variant has not been reported in the literature in individuals affected with CASR-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 563 of the CASR protein (p.Phe563Ser).

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.