NM_000388.4(CASR):c.2303G>T (p.Gly768Val) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Oct 29, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001238616.1

Allele description [Variation Report for NM_000388.4(CASR):c.2303G>T (p.Gly768Val)]

NM_000388.4(CASR):c.2303G>T (p.Gly768Val)

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.2303G>T (p.Gly768Val)
HGVS:
  • NC_000003.12:g.122284257G>T
  • NG_009058.1:g.105575G>T
  • NM_000388.4:c.2303G>TMANE SELECT
  • NM_001178065.2:c.2333G>T
  • NP_000379.3:p.Gly768Val
  • NP_001171536.2:p.Gly778Val
  • NC_000003.11:g.122003104G>T
  • NM_000388.3:c.2303G>T
Protein change:
G768V
Links:
dbSNP: rs201858689
NCBI 1000 Genomes Browser:
rs201858689
Molecular consequence:
  • NM_000388.4:c.2303G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178065.2:c.2333G>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:
Hypocalcemia, autosomal dominant 1 (HYPOC1)
Synonyms:
HYPERCALCIURIC HYPOCALCEMIA; 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
SCV001411439Invitaecriteria provided, single submitter
Uncertain significance
(Oct 29, 2019)
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

A novel CASR mutation associated with neonatal severe hyperparathyroidism transmitted as an autosomal recessive disorder.

Diaz-Thomas A, Cannon J, Iyer P, Al-Maawali A, Fazalullah M, Diamond F, Mueller OT, Root AW, Alyaarubi S.

J Pediatr Endocrinol Metab. 2014 Sep;27(9-10):851-6. doi: 10.1515/jpem-2013-0343.

PubMed [citation]
PMID:
24854525

Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites.

Hannan FM, Nesbit MA, Zhang C, Cranston T, Curley AJ, Harding B, Fratter C, Rust N, Christie PT, Turner JJ, Lemos MC, Bowl MR, Bouillon R, Brain C, Bridges N, Burren C, Connell JM, Jung H, Marks E, McCredie D, Mughal Z, Rodda C, et al.

Hum Mol Genet. 2012 Jun 15;21(12):2768-78. doi: 10.1093/hmg/dds105. Epub 2012 Mar 14.

PubMed [citation]
PMID:
22422767
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001411439.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces glycine with valine at codon 768 of the CASR protein (p.Gly768Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs201858689, ExAC 0.03%). This variant has been observed to segregate with CASR-related disease in a family (PMID: 24854525), and has been reported in an individual affected with neonatal severe primary hyperparathyroidism (NSHPT) (PMID: 22422767). ClinVar contains an entry for this variant (Variation ID: 633483). This variant has been reported to have insufficient data to determine the effect on CASR protein function (PMID: 24854525). 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.

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

Last Updated: Oct 7, 2021

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