NM_000388.4(CASR):c.1393C>T (p.Arg465Trp) AND Epilepsy, idiopathic generalized, susceptibility to, 8

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 5, 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:: RCV001824137.10

Allele description [Variation Report for NM_000388.4(CASR):c.1393C>T (p.Arg465Trp)]

NM_000388.4(CASR):c.1393C>T (p.Arg465Trp)

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.1393C>T (p.Arg465Trp)

Other names:

p.Arg465Trp

HGVS:

NC_000003.12:g.122275827C>T
NG_009058.1:g.97145C>T
NM_000388.4:c.1393C>TMANE SELECT
NM_001178065.2:c.1393C>T
NP_000379.3:p.Arg465Trp
NP_001171536.2:p.Arg465Trp
NC_000003.11:g.121994674C>T
NM_000388.3:c.1393C>T

Protein change:

R465W

Links:

dbSNP: rs751217000

NCBI 1000 Genomes Browser:

rs751217000

Molecular consequence:

NM_000388.4:c.1393C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001178065.2:c.1393C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Epilepsy, idiopathic generalized, susceptibility to, 8
Synonyms:: Epilepsy, idiopathic generalized 8
Identifiers:: MONDO: MONDO:0013032; MedGen: C2752062; OMIM: 612899

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002073747	DASA	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 5, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20164288, 29026550, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002073747

DASA

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 5, 2022)

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	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Calcium-sensing receptor (CASR) mutations in hypercalcemic states: studies from a single endocrine clinic over three years.

Guarnieri V, Canaff L, Yun FH, Scillitani A, Battista C, Muscarella LA, Wong BY, Notarangelo A, D'Agruma L, Sacco M, Cole DE, Hendy GN.

J Clin Endocrinol Metab. 2010 Apr;95(4):1819-29. doi: 10.1210/jc.2008-2430. Epub 2010 Feb 17.

PubMed [citation]

PMID:: 20164288

Making (mis) sense of asymptomatic marked hypercalcemia in pregnancy.

Maltese G, Izatt L, McGowan BM, Hafeez K, Hubbard JG, Carroll PV.

Clin Case Rep. 2017 Oct;5(10):1587-1590. doi: 10.1002/ccr3.1074.

PubMed [citation]

PMID:: 29026550
PMCID:: PMC5628236

See all PubMed Citations (3)

Details of each submission

From DASA, SCV002073747.1

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

Description

The c.1393C>T;p.(Arg465Trp) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (PMID: 20164288) - PS4_supporting. Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 29026550) - PS3_supporting. The variant is present at low allele frequencies population databases (rs751217000 – gnomAD 0.00006570%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. Pathogenic missense variant in this residue have been reported (ClinVar ID: 8352 - c.1394G>A (p.Arg465Gln)) - PM5. The variant co-segregated with disease in multiple affected family members (PMID: 29026550) - PP1_supporting. In summary, the currently available evidence indicates that the variant is likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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