ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.889G>A (p.Glu297Lys) (rs121909259)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701654 SCV000830466 pathogenic Hypocalciuric hypercalcemia, familial, type 1; Hypocalcemia, autosomal dominant 1 2018-03-05 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 297 of the CASR protein (p.Glu297Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with familial hypocalciuric hypercalcemia (FHH) and segregates with FHH in several families (PMID: 16642557, 19423559, 7916660). This variant has also been reported in the homozygous state in an individual affected with neonatal severe hyperparathyroidism (PMID: 7916660). This variant is also known as E298K in the literature. ClinVar contains an entry for this variant (Variation ID: 8313). Experimental studies have shown that this missense change results in reduced localization of the calcium sensing receptor to the plasma membrane, as well as, reduced response to extracellular calcium concentrations (PMID: 23077345, 12114500, 27434672, 12095982). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000008811 SCV000029021 pathogenic Hypocalciuric hypercalcemia, familial, type 1 2006-04-30 no assertion criteria provided literature only
OMIM RCV000008812 SCV000029022 pathogenic Neonatal severe hyperparathyroidism 2006-04-30 no assertion criteria provided literature only

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