ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.680G>T (p.Arg227Leu) (rs28936684)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001384282 SCV001583724 pathogenic Familial hypocalciuric hypercalcemia; Hypocalcemia, autosomal dominant 1 2020-04-02 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 227 of the CASR protein (p.Arg227Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with familial hypocalciuric hypercalcemia and de novo in an individual with neonatal hyperparathyroidism (PMID: 8675635, 26963950). ClinVar contains an entry for this variant (Variation ID: 8317). This variant has been reported to affect CASR protein function (PMID: 8878438, 15572418, 27666534). This variant disrupts the p.227 amino acid residue in CASR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22422767, 26963950, 7726161, 1302026, 15572418). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000008818 SCV000029028 pathogenic Neonatal severe hyperparathyroidism 2005-02-01 no assertion criteria provided literature only

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