Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000517631 | SCV000612681 | uncertain significance | not specified | 2016-12-05 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000517631 | SCV004099759 | uncertain significance | not specified | 2023-09-12 | criteria provided, single submitter | clinical testing | Variant summary: CASR c.89G>A (p.Gly30Glu) results in a non-conservative amino acid change located in the ligand binding region (IPR001828) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251336 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.89G>A in individuals affected with Autosomal Dominant Hypocalcemia and no experimental evidence demonstrating its impact on protein function have been reported. However, several missense changes affecting nearby residues (e.g. A26G/S, Q27R/E/P, K29E, I32V, L37P) are reported in affected individuals (HGMD), indicating a functional importance for this protein region. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Invitae | RCV003766914 | SCV004570747 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2023-07-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 30 of the CASR protein (p.Gly30Glu). This variant is not present in population databases (gnomAD no frequency). 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: 447004). 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. 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. |