NM_000388.4(CASR):c.2682_3224del (p.Ser895_Val1075del) AND Autosomal dominant hypocalcemia 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 1, 2000
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000008841.5

Allele description [Variation Report for NM_000388.4(CASR):c.2682_3224del (p.Ser895_Val1075del)]

NM_000388.4(CASR):c.2682_3224del (p.Ser895_Val1075del)

Gene:

CASR:calcium sensing receptor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3q13.3-q21

Genomic location:

Preferred name:

NM_000388.4(CASR):c.2682_3224del (p.Ser895_Val1075del)

HGVS:

NC_000003.12:g.122284636_122285178del
NG_009058.2:g.105969_106511del
NM_000388.4:c.2682_3224delMANE SELECT
NM_001178065.2:c.2712_3254del
NP_000379.3:p.Ser895_Val1075del
NP_001171536.2:p.Ser905_Val1085del
NC_000003.11:g.122003483_122004025del
NG_009058.1:g.105954_106496del
NM_000388.3:c.2682_3224del

Note:

NCBI staff reviewed the sequence information reported in PubMed 10770217 Fig. 2 to determine the location of this deletion on the current reference sequence.

Links:

OMIM: 601199.0030; dbSNP: rs1553769169

NCBI 1000 Genomes Browser:

rs1553769169

Molecular consequence:

NM_000388.4:c.2682_3224del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001178065.2:c.2712_3254del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Autosomal dominant hypocalcemia 1 (HYPOC1)
Synonyms:: HYPOCALCEMIA, FAMILIAL
Identifiers:: MONDO: MONDO:0011013; MedGen: C0342345; OMIM: 601198

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000029051	OMIM	no assertion criteria provided	Pathogenic (Apr 1, 2000)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000029051

OMIM

no assertion criteria provided

Pathogenic
(Apr 1, 2000)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

A large homozygous or heterozygous in-frame deletion within the calcium-sensing receptor's carboxylterminal cytoplasmic tail that causes autosomal dominant hypocalcemia.

Lienhardt A, Garabédian M, Bai M, Sinding C, Zhang Z, Lagarde JP, Boulesteix J, Rigaud M, Brown EM, Kottler ML.

J Clin Endocrinol Metab. 2000 Apr;85(4):1695-702.

PubMed [citation]

PMID:: 10770217

Details of each submission

From OMIM, SCV000029051.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

Lienhardt et al. (2000) reported a 3-generation family with autosomal dominant hypocalcemia (HYPOC1; 601198) caused by a large in-frame deletion of 181 amino acids in the C-terminal tail of CASR from ser895 to val1075. The affected grandfather was homozygous for the deletion but was not more severely affected than the heterozygous affected individuals. Functional properties of mutant and wildtype CASRs were studied in transiently transfected fura-2-loaded HEK293 cells. The mutant CASR exhibited a gain of function, but there was no difference between cells transfected with mutant cDNA alone or cotransfected with mutant and wildtype cDNAs, consistent with the similar phenotypes of heterozygous and homozygous family members. The authors concluded that this activating deletion may exert a dominant-positive effect on the wildtype CASR. The cell surface expression of the mutant CASR was greater than that of the wildtype CASR, potentially contributing to its gain of function.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 5, 2023

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