ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.1174C>T (p.Arg392Ter)

dbSNP: rs1559959758
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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, Department of Genetics, University Medical Center Groningen RCV000760418 SCV001744077 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000760418 SCV001960016 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000760418 SCV001972879 pathogenic not provided no assertion criteria provided clinical testing

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