NM_000388.4(CASR):c.2335T>C (p.Tyr779His) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 25, 2021
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:: RCV001779514.1

Allele description [Variation Report for NM_000388.4(CASR):c.2335T>C (p.Tyr779His)]

NM_000388.4(CASR):c.2335T>C (p.Tyr779His)

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.2335T>C (p.Tyr779His)

HGVS:

NC_000003.12:g.122284289T>C
NG_009058.2:g.105622T>C
NM_000388.4:c.2335T>CMANE SELECT
NM_001178065.2:c.2365T>C
NP_000379.3:p.Tyr779His
NP_001171536.2:p.Tyr789His
NC_000003.11:g.122003136T>C
NG_009058.1:g.105607T>C
NM_000388.3:c.2335T>C

Protein change:

Y779H

Links:

dbSNP: rs766889439

NCBI 1000 Genomes Browser:

rs766889439

Molecular consequence:

NM_000388.4:c.2335T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001178065.2:c.2365T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002015062	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Oct 25, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002015062

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Oct 25, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Expanding the spectrum of genetic variants in the calcium-sensing receptor (CASR) gene in hypercalcemic individuals.

Nissen PH, Rejnmark L.

Clin Endocrinol (Oxf). 2019 Nov;91(5):683-690. doi: 10.1111/cen.14078. Epub 2019 Sep 9.

PubMed [citation]

PMID:: 31433865

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002015062.1

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

Description

Variant summary: CASR c.2335T>C (p.Tyr779His) results in a conservative amino acid change located in the GPCR family 3, C-terminal domain (IPR017978) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251134 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2335T>C has been reported in the literature in an individual affected with hypercalcemia (Nissen_2019). This report does not provide unequivocal conclusions about association of the variant with Familial Hypocalciuric Hypercalcemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as 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: Dec 24, 2023

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