ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.679C>T (p.Arg227Ter) (rs1085307984)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000639467 SCV000761042 pathogenic Familial hypocalciuric hypercalcemia; Hypocalcemia, autosomal dominant 1 2018-11-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg227*) in the CASR gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with neonatal severe primary hyperparathyroidism and familial hypocalciuric hypercalcemia  (PMID: 20972686, 27666534, 26963950). Loss-of-function variants in CASR are known to be pathogenic (PMID: 22422767). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000657571 SCV000779308 pathogenic not provided 2018-05-06 criteria provided, single submitter clinical testing The R227X nonsense variant in the CASR gene has been reported previously in association with familial hypocalciuric hypercalcemia, as well as with neonatal severe primary hyperparathyroidism when observed in the homozygous state (Vargas-Poussou et al., 2016; Al-Khalaf et al., 2011). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is not observed in large population cohorts (Lek et al., 2016). In summary, we consider this variant to be pathogenic.
Athena Diagnostics Inc RCV000657571 SCV001143444 pathogenic not provided 2018-10-09 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data. Damaging to protein function(s) relevant to disease mechanism.
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV000657571 SCV001449731 likely pathogenic not provided 2018-12-11 criteria provided, single submitter clinical testing

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