Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000760418 | SCV000890296 | pathogenic | not provided | 2018-06-01 | criteria provided, single submitter | clinical testing | The R392X nonsense variant in the CASR gene has been reported previously in association with neonatal severe primary hyperparathyroidism when observed in the homozygous state, however, heterozygous carrier parents were unaffected and had calcium levels within normal limits (Hannan et al., 2012; Ward et al., 2013). The variant is not observed in large population cohorts (Lek et al., 2016). Functional studies show that R392X results in poor localization compared to wildtype and an absence of activity in response to calcium (Ward et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we consider this to be a pathogenic variant. |
Invitae | RCV003768284 | SCV004573234 | pathogenic | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2023-07-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg392*) in the CASR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CASR are known to be pathogenic (PMID: 11807402, 14985373, 22422767). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with neonatal severe hyperparathyroidism (PMID: 22422767). ClinVar contains an entry for this variant (Variation ID: 620132). For these reasons, this variant has been classified as Pathogenic. |
Diagnostic Laboratory, |
RCV000760418 | SCV001744077 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000760418 | SCV001960016 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000760418 | SCV001972879 | pathogenic | not provided | no assertion criteria provided | clinical testing |