NM_000388.4(CASR):c.475C>G (p.Leu159Val) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 27, 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:: RCV001062371.9

Allele description [Variation Report for NM_000388.4(CASR):c.475C>G (p.Leu159Val)]

NM_000388.4(CASR):c.475C>G (p.Leu159Val)

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.475C>G (p.Leu159Val)

HGVS:

NC_000003.12:g.122257370C>G
NG_009058.2:g.78703C>G
NM_000388.4:c.475C>GMANE SELECT
NM_001178065.2:c.475C>G
NP_000379.3:p.Leu159Val
NP_001171536.2:p.Leu159Val
NC_000003.11:g.121976217C>G
NG_009058.1:g.78688C>G
NM_000388.3:c.475C>G

Protein change:

L159V

Links:

dbSNP: rs767329910

NCBI 1000 Genomes Browser:

rs767329910

Molecular consequence:

NM_000388.4:c.475C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001178065.2:c.475C>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001227166	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 27, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21175100, 27666534, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001227166

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 27, 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

Kabuki syndrome and Crohn disease in a child with familial hypocalciuric hypercalcemia.

Ho J, Fox D, Innes AM, McLeod R, Butzner D, Johnson N, Trevenen C, Kendrick V, Cole DE.

J Pediatr Endocrinol Metab. 2010 Sep;23(9):975-9.

PubMed [citation]

PMID:: 21175100

Heterozygous inactivating CaSR mutations causing neonatal hyperparathyroidism: function, inheritance and phenotype.

Glaudo M, Letz S, Quinkler M, Bogner U, Elbelt U, Strasburger CJ, Schnabel D, Lankes E, Scheel S, Feldkamp J, Haag C, Schulze E, Frank-Raue K, Raue F, Mayr B, Schöfl C.

Eur J Endocrinol. 2016 Nov;175(5):421-31. doi: 10.1530/EJE-16-0223.

PubMed [citation]

PMID:: 27666534

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001227166.5

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

Description

This variant is present in population databases (rs767329910, gnomAD 0.0009%). 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. This variant disrupts the p.Leu159 amino acid residue in CASR. Other variant(s) that disrupt this residue have been observed in individuals with CASR-related conditions (PMID: 21175100, 27666534), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 856823). This variant has not been reported in the literature in individuals affected with CASR-related conditions. This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 159 of the CASR protein (p.Leu159Val).

#	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: Sep 29, 2024

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