NM_000388.3(CASR):c.1942C>T (p.Arg648Ter) AND Hypocalciuric hypercalcemia, familial, type 1

Clinical significance:Pathogenic (Last evaluated: Aug 1, 2004)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000008843.5

Allele description

NM_000388.3(CASR):c.1942C>T (p.Arg648Ter)

Gene:
CASR:calcium sensing receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q21.1
Genomic location:
Preferred name:
NM_000388.3(CASR):c.1942C>T (p.Arg648Ter)
HGVS:
  • NC_000003.12:g.122283896C>T
  • NG_009058.1:g.105214C>T
  • NM_000388.3:c.1942C>T
  • NP_000379.2:p.Arg648Ter
  • NC_000003.11:g.122002743C>T
Protein change:
R648*; ARG648TER
Links:
OMIM: 601199.0032; dbSNP: rs104893705
NCBI 1000 Genomes Browser:
rs104893705
Molecular consequence:
  • NM_000388.3:c.1942C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Hypocalciuric hypercalcemia, familial, type 1 (HHC1)
Synonyms:
Familial benign hypercalcemia; HHC
Identifiers:
MedGen: C0342637; Orphanet: 405; Orphanet: 93372; OMIM: 145980

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000029053OMIMno assertion criteria providedPathogenic
(Aug 1, 2004)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A novel mutation in the calcium-sensing receptor gene in a Chinese subject with persistent hypercalcemia and hypocalciuria.

Jap TS, Wu YC, Jenq SF, Won GS.

J Clin Endocrinol Metab. 2001 Jan;86(1):13-5.

PubMed [citation]
PMID:
11231970

Functional deletion of the calcium-sensing receptor in a case of neonatal severe hyperparathyroidism.

Ward BK, Magno AL, Davis EA, Hanyaloglu AC, Stuckey BG, Burrows M, Eidne KA, Charles AK, Ratajczak T.

J Clin Endocrinol Metab. 2004 Aug;89(8):3721-30.

PubMed [citation]
PMID:
15292296

Details of each submission

From OMIM, SCV000029053.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

Jap et al. (2001) studied a 79-year-old male with hypocalciuric hypercalcemia (145980) without sibs or children. DNA sequence analysis of the CASR gene showed that the proband was heterozygous for a CGA-to-TGA transition in exon 7 of the CASR gene that encoded an arg648-to-ter (R648X) mutation. This mutation, located in the C terminus of the first intracellular loop of the calcium-sensing receptor, predicts a markedly truncated protein. The mutation was not found in a control group of 50 normal Chinese subjects in Taiwan.

Ward et al. (2004) found this mutation in compound heterozygosity with a G94X truncation of the receptor (601199.0042) in an Australian infant with neonatal severe hyperparathyroidism (NSHPT; 239200). Confocal microscopy demonstrated that the R648X receptor was present in the cytoplasm and also associated with the cell membrane. Functional assays in which R648X and wildtype receptor were cotransfected into HEK293 cells demonstrated a reduction in wildtype Ca(2+) responsiveness by the R648X receptor, even at physiologic Ca(2+) levels, thus simulating familial hypocalciuric hypercalcemia (145980) in relatives of the infant who were heterozygous for the R648X mutation. The R648X receptor alone was nonresponsive to Ca(2+).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 23, 2018

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