NM_000388.4(CASR):c.2687G>A (p.Arg896His) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 10, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000468483.14

Allele description

NM_000388.4(CASR):c.2687G>A (p.Arg896His)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

3q21.1

Genomic location:

Preferred name:

NM_000388.4(CASR):c.2687G>A (p.Arg896His)

HGVS:

NC_000003.12:g.122284641G>A
NG_009058.1:g.105959G>A
NM_000388.4:c.2687G>AMANE SELECT
NM_001178065.2:c.2717G>A
NP_000379.3:p.Arg896His
NP_001171536.2:p.Arg906His
NC_000003.11:g.122003488G>A
NM_000388.3:c.2687G>A

Protein change:

R896H

Links:

dbSNP: rs773552397

NCBI 1000 Genomes Browser:

rs773552397

Molecular consequence:

NM_000388.4:c.2687G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001178065.2:c.2717G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial hypocalciuric hypercalcemia (FHH)
Synonyms:: Familial benign hypercalcemia
Identifiers:: MONDO: MONDO:0018458; MedGen: C1809471; OMIM: PS145980

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

Recent activity

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phage tail assembly chaperone G [Escherichia coli]
phage tail assembly chaperone G [Escherichia coli]
gi|446401190|ref|WP_000479045.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000551003	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16497624, 20798521, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000551003

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 10, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the calcium-sensing receptor: a new genetic risk factor for chronic pancreatitis?

Felderbauer P, Klein W, Bulut K, Ansorge N, Dekomien G, Werner I, Epplen JT, Schmitz F, Schmidt WE.

Scand J Gastroenterol. 2006 Mar;41(3):343-8.

PubMed [citation]

PMID:: 16497624

Calcium sensing receptor mutations implicated in pancreatitis and idiopathic epilepsy syndrome disrupt an arginine-rich retention motif.

Stepanchick A, McKenna J, McGovern O, Huang Y, Breitwieser GE.

Cell Physiol Biochem. 2010;26(3):363-74. doi: 10.1159/000320560. Epub 2010 Aug 24.

PubMed [citation]

PMID:: 20798521
PMCID:: PMC3709174

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000551003.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 896 of the CASR protein (p.Arg896His). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with pancreatitis (PMID: 16497624). ClinVar contains an entry for this variant (Variation ID: 410364). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects CASR function (PMID: 20798521). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 16, 2024

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