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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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001227166Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jun 27, 2023)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024