NM_000388.4(CASR):c.2008G>C (p.Gly670Arg) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 27, 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:: RCV001912618.3

Allele description [Variation Report for NM_000388.4(CASR):c.2008G>C (p.Gly670Arg)]

NM_000388.4(CASR):c.2008G>C (p.Gly670Arg)

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.2008G>C (p.Gly670Arg)

HGVS:

NC_000003.12:g.122283962G>C
NG_009058.2:g.105295G>C
NM_000388.4:c.2008G>CMANE SELECT
NM_001178065.2:c.2038G>C
NP_000379.3:p.Gly670Arg
NP_001171536.2:p.Gly680Arg
NC_000003.11:g.122002809G>C
NG_009058.1:g.105280G>C

Protein change:

G670R

Links:

dbSNP: rs2074927550

NCBI 1000 Genomes Browser:

rs2074927550

Molecular consequence:

NM_000388.4:c.2008G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001178065.2:c.2038G>C - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002170379	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 27, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 8675635, 17698911, 26963950, 32347971, 22798347, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002170379

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 27, 2022)

germline

clinical testing

PubMed (6)
[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 mutations in familial benign hypercalcemia and neonatal hyperparathyroidism.

Pearce SH, Trump D, Wooding C, Besser GM, Chew SL, Grant DB, Heath DA, Hughes IA, Paterson CR, Whyte MP, et al.

J Clin Invest. 1995 Dec;96(6):2683-92.

PubMed [citation]

PMID:: 8675635
PMCID:: PMC185975

Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population.

Nissen PH, Christensen SE, Heickendorff L, Brixen K, Mosekilde L.

J Clin Endocrinol Metab. 2007 Nov;92(11):4373-9. Epub 2007 Aug 14.

PubMed [citation]

PMID:: 17698911

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV002170379.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This missense change has been observed in individuals with clinical features of familial hypocalciuric hypercalcemia (PMID: 8675635, 17698911, 26963950, 32347971; Invitae). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CASR function (PMID: 22798347). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 670 of the CASR protein (p.Gly670Arg).

#	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: Feb 28, 2024

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