NM_000388.4(CASR):c.2036T>G (p.Leu679Arg) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 22, 2017
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:: RCV002232607.14

Allele description [Variation Report for NM_000388.4(CASR):c.2036T>G (p.Leu679Arg)]

NM_000388.4(CASR):c.2036T>G (p.Leu679Arg)

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.2036T>G (p.Leu679Arg)

HGVS:

NC_000003.12:g.122283990T>G
NG_009058.1:g.105308T>G
NM_000388.4:c.2036T>GMANE SELECT
NM_001178065.2:c.2066T>G
NP_000379.3:p.Leu679Arg
NP_001171536.2:p.Leu689Arg
NC_000003.11:g.122002837T>G
NM_000388.3:c.2036T>G

Protein change:

L679R

Links:

dbSNP: rs1553768983

NCBI 1000 Genomes Browser:

rs1553768983

Molecular consequence:

NM_000388.4:c.2036T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001178065.2:c.2066T>G - 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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The abundantly expressed microRNA locus miR-144/451 regulates only about 100 tar...
The abundantly expressed microRNA locus miR-144/451 regulates only about 100 target mRNAs during erythroid development [RNA-seq]
The abundantly expressed microRNA locus miR-144/451 regulates only about 100 target mRNAs during erythroid development [RNA-seq]

BioProject
mediator of RNA polymerase II transcription subunit 12-like protein isoform X5 [...
mediator of RNA polymerase II transcription subunit 12-like protein isoform X5 [Homo sapiens]
gi|2462586941|ref|XP_054201123.1|

Protein
PREDICTED: Homo sapiens mediator complex subunit 12L (MED12L), transcript varian...
PREDICTED: Homo sapiens mediator complex subunit 12L (MED12L), transcript variant X1, mRNA
gi|2217341695|ref|XM_017005676.2|

Nucleotide
PREDICTED: Homo sapiens mediator complex subunit 12L (MED12L), transcript varian...
PREDICTED: Homo sapiens mediator complex subunit 12L (MED12L), transcript variant X2, mRNA
gi|2462586930|ref|XM_054345143.1|

Nucleotide
PREDICTED: Drosophila sechellia polypeptide N-acetylgalactosaminyltransferase 5 ...
PREDICTED: Drosophila sechellia polypeptide N-acetylgalactosaminyltransferase 5 (LOC6613446), transcript variant X3, mRNA
gi|1818115582|ref|XM_032713978.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000761015	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 22, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000761015

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 22, 2017)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000761015.4

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

Description

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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CASR-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with arginine at codon 679 of the CASR protein (p.Leu679Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine.

#	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: Nov 10, 2024

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