NM_000388.4(CASR):c.197G>T (p.Arg66Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 25, 2020
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:: RCV001372372.7

Allele description [Variation Report for NM_000388.4(CASR):c.197G>T (p.Arg66Leu)]

NM_000388.4(CASR):c.197G>T (p.Arg66Leu)

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.197G>T (p.Arg66Leu)

HGVS:

NC_000003.12:g.122257092G>T
NG_009058.1:g.78410G>T
NM_000388.4:c.197G>TMANE SELECT
NM_001178065.2:c.197G>T
NP_000379.3:p.Arg66Leu
NP_001171536.2:p.Arg66Leu
NC_000003.11:g.121975939G>T
NM_000388.2:c.197G>T
NM_000388.3:c.197G>T

Protein change:

R66L

Links:

dbSNP: rs1276839362

NCBI 1000 Genomes Browser:

rs1276839362

Molecular consequence:

NM_000388.4:c.197G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001178065.2:c.197G>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

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

Recent activity

Clear Turn Off Turn On

Full text in PMC (nucleotide) for Gene (Select 9702) (127)
PMC
Conserved Domain Links for Gene (Select 856251) (1)
Conserved Domains

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
SCV001569016	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 25, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16740594, 25104082, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001569016

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 25, 2020)

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

Calcium-sensing receptor dimerizes in the endoplasmic reticulum: biochemical and biophysical characterization of CASR mutants retained intracellularly.

Pidasheva S, Grant M, Canaff L, Ercan O, Kumar U, Hendy GN.

Hum Mol Genet. 2006 Jul 15;15(14):2200-9. Epub 2006 Jun 1.

PubMed [citation]

PMID:: 16740594

Calcium-sensing-related gene mutations in hypercalcaemic hypocalciuric patients as differential diagnosis from primary hyperparathyroidism: detection of two novel inactivating mutations in an Italian population.

Stratta P, Merlotti G, Musetti C, Quaglia M, Pagani A, Izzo C, Radin E, Airoldi A, Baorda F, Palladino T, Leone MP, Guarnieri V.

Nephrol Dial Transplant. 2014 Oct;29(10):1902-9. doi: 10.1093/ndt/gfu065. Epub 2014 Aug 7.

PubMed [citation]

PMID:: 25104082

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001569016.4

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). This variant disrupts the p.Arg66 amino acid residue in CASR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16740594, 25104082). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has not been reported in the literature in individuals with CASR-related conditions. ClinVar contains an entry for this variant (Variation ID: 585620). This sequence change replaces arginine with leucine at codon 66 of the CASR protein (p.Arg66Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency).

#	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: Oct 26, 2024

ClinVar

Relating variation to medicine