ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.1942C>T (p.Arg648Ter) (rs104893705)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001013794 SCV001174424 pathogenic Inborn genetic diseases 2019-03-13 criteria provided, single submitter clinical testing The p.R648* pathogenic mutation (also known as c.1942C>T), located in coding exon 6 of the CASR gene, results from a C to T substitution at nucleotide position 1942. This changes the amino acid from an arginine to a stop codon within coding exon 6. This mutation has been reported in a few individuals with familial hypocalciuric hypercalcemia and segregated with disease in one large family (Jap TS et al. J. Clin. Endocrinol. Metab., 2001 Jan;86:13-5; Yamauchi M et al. J. Bone Miner. Res., 2002 Dec;17:2174-82). This mutation was also confirmed in trans in conjunction with another nonsense variant in an infant with neonatal severe hyperparathyroidism (Ward BK et al. J. Clin. Endocrinol. Metab., 2004 Aug;89:3721-30). In HEK293 cells, this mutation showed no response to high calcium levels compared to wild type (Yamauchi M et al. J. Bone Miner. Res., 2002 Dec;17:2174-82; Ward BK et al. J. Clin. Endocrinol. Metab., 2004 Aug;89:3721-30; Nakamura A et al. J. Clin. Endocrinol. Metab., 2013 Oct;98:E1692-701). This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
OMIM RCV000008843 SCV000029053 pathogenic Hypocalciuric hypercalcemia, familial, type 1 2004-08-01 no assertion criteria provided literature only
OMIM RCV000054484 SCV000082961 pathogenic Neonatal severe hyperparathyroidism 2004-08-01 no assertion criteria provided literature only

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