NM_000388.4(CASR):c.2237C>T (p.Ala746Val) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 1, 2023
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:: RCV000539780.10

Allele description [Variation Report for NM_000388.4(CASR):c.2237C>T (p.Ala746Val)]

NM_000388.4(CASR):c.2237C>T (p.Ala746Val)

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.2237C>T (p.Ala746Val)

HGVS:

NC_000003.12:g.122284191C>T
NG_009058.1:g.105509C>T
NM_000388.4:c.2237C>TMANE SELECT
NM_001178065.1:c.2267C>T
NM_001178065.2:c.2267C>T
NP_000379.3:p.Ala746Val
NP_001171536.2:p.Ala756Val
NC_000003.11:g.122003038C>T
NM_000388.3:c.2237C>T

Protein change:

A746V

Links:

dbSNP: rs139417576

NCBI 1000 Genomes Browser:

rs139417576

Molecular consequence:

NM_000388.4:c.2237C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001178065.2:c.2267C>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000638040	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 1, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26963950, 31672324, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000638040

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 1, 2023)

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

Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences.

Vargas-Poussou R, Mansour-Hendili L, Baron S, Bertocchio JP, Travers C, Simian C, Treard C, Baudouin V, Beltran S, Broux F, Camard O, Cloarec S, Cormier C, Debussche X, Dubosclard E, Eid C, Haymann JP, Kiando SR, Kuhn JM, Lefort G, Linglart A, Lucas-Pouliquen B, et al.

J Clin Endocrinol Metab. 2016 May;101(5):2185-95. doi: 10.1210/jc.2015-3442. Epub 2016 Mar 10.

PubMed [citation]

PMID:: 26963950

High-throughput sequencing contributes to the diagnosis of tubulopathies and familial hypercalcemia hypocalciuria in adults.

Hureaux M, Ashton E, Dahan K, Houillier P, Blanchard A, Cormier C, Koumakis E, Iancu D, Belge H, Hilbert P, Rotthier A, Del Favero J, Schaefer F, Kleta R, Bockenhauer D, Jeunemaitre X, Devuyst O, Walsh SB, Vargas-Poussou R.

Kidney Int. 2019 Dec;96(6):1408-1416. doi: 10.1016/j.kint.2019.08.027. Epub 2019 Sep 16.

PubMed [citation]

PMID:: 31672324

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000638040.8

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 746 of the CASR protein (p.Ala746Val). This variant is present in population databases (rs139417576, gnomAD 0.05%). This missense change has been observed in individual(s) with familial hypocalciuric hypercalcemia (PMID: 26963950, 31672324). ClinVar contains an entry for this variant (Variation ID: 463921). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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.

#	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

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