NM_000388.4(CASR):c.2393C>T (p.Pro798Leu) AND Familial hypocalciuric hypercalcemia

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 3, 2022
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:: RCV002265771.2

Allele description [Variation Report for NM_000388.4(CASR):c.2393C>T (p.Pro798Leu)]

NM_000388.4(CASR):c.2393C>T (p.Pro798Leu)

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.2393C>T (p.Pro798Leu)

HGVS:

NC_000003.12:g.122284347C>T
NG_009058.1:g.105665C>T
NM_000388.4:c.2393C>TMANE SELECT
NM_001178065.2:c.2423C>T
NP_000379.3:p.Pro798Leu
NP_001171536.2:p.Pro808Leu
NC_000003.11:g.122003194C>T
NM_000388.3:c.2393C>T

Protein change:

P798L

Links:

dbSNP: rs1060502856

NCBI 1000 Genomes Browser:

rs1060502856

Molecular consequence:

NM_000388.4:c.2393C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001178065.2:c.2423C>T - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002548002	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (May 3, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 31672324, 22422767, 31189130, 32430905 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002548002

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(May 3, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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

High-throughput sequencing contributes to the diagnosis of tubulopathies and familial hypercalcemia hypocalciuria in adults.

Hureaux M, Ashton E, Dahan K, Houillier P, Blanchard A, Cormier C, Koumakis E, Iancu D, Belge H, Hilbert P, Rotthier A, Del Favero J, Schaefer F, Kleta R, Bockenhauer D, Jeunemaitre X, Devuyst O, Walsh SB, Vargas-Poussou R.

Kidney Int. 2019 Dec;96(6):1408-1416. doi: 10.1016/j.kint.2019.08.027. Epub 2019 Sep 16.

PubMed [citation]

PMID:: 31672324

Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites.

Hannan FM, Nesbit MA, Zhang C, Cranston T, Curley AJ, Harding B, Fratter C, Rust N, Christie PT, Turner JJ, Lemos MC, Bowl MR, Bouillon R, Brain C, Bridges N, Burren C, Connell JM, Jung H, Marks E, McCredie D, Mughal Z, Rodda C, et al.

Hum Mol Genet. 2012 Jun 15;21(12):2768-78. doi: 10.1093/hmg/dds105. Epub 2012 Mar 14.

PubMed [citation]

PMID:: 22422767

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002548002.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Variant summary: CASR c.2393C>T (p.Pro798Leu) results in a non-conservative amino acid change located in the GPCR family 3, C-terminal domain (IPR017978) of the encoded protein sequence. Proline 798 is conserved among different species, suggesting its crucial role in the normal functioning of CASRs. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251304 control chromosomes. c.2393C>T has been reported in the literature in individuals affected with Familial Hypocalciuric Hypercalcemia (example, Hannan_2012, Hureaux_2019, Gorvin_2019, Mariathasan_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	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 29, 2024

ClinVar

Relating variation to medicine