Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000484137 | SCV000568683 | uncertain significance | not provided | 2019-09-18 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in individuals with suspected familial hypocalciuric hypercalcemia (Nissen 2007, Vargas-Poussou 2016); This variant is associated with the following publications: (PMID: 17698911, 26963950) |
Labcorp Genetics |
RCV000527853 | SCV000638079 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 21 of the CASR protein (p.Gly21Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with familial hypocalciuric hypercalcemia (PMID: 17698911, 26963950). ClinVar contains an entry for this variant (Variation ID: 420105). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Athena Diagnostics | RCV000484137 | SCV001477110 | likely pathogenic | not provided | 2023-08-11 | criteria provided, single submitter | clinical testing | This variant has been identified in multiple unrelated individuals with clinical features associated with autosomal dominant hypocalciuric hypercalcemia. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging. |
Clinical Genetics Laboratory, |
RCV000484137 | SCV005197385 | likely pathogenic | not provided | 2024-03-26 | criteria provided, single submitter | clinical testing |