U.S. flag

An official website of the United States government

  • delete

NM_000388.4(CASR):c.496A>G (p.Ser166Gly) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 25, 2017
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:
RCV000639468.1

Allele description

NM_000388.4(CASR):c.496A>G (p.Ser166Gly)

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.496A>G (p.Ser166Gly)
HGVS:
  • NC_000003.12:g.122261531A>G
  • NG_009058.1:g.82849A>G
  • NM_000388.4:c.496A>GMANE SELECT
  • NM_001178065.2:c.496A>G
  • NP_000379.3:p.Ser166Gly
  • NP_001171536.2:p.Ser166Gly
  • NC_000003.11:g.121980378A>G
  • NM_000388.3:c.496A>G
Protein change:
S166G
Links:
dbSNP: rs193922441
NCBI 1000 Genomes Browser:
rs193922441
Molecular consequence:
  • NM_000388.4:c.496A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178065.2:c.496A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial hypocalciuric hypercalcemia 1
Synonyms:
Hypercalcemia, familial benign type 1
Identifiers:
MONDO: MONDO:0007791; MedGen: C0342637; Orphanet: 405; Orphanet: 93372; OMIM: 145980
Name:
Autosomal dominant hypocalcemia 1
Synonyms:
HYPOCALCEMIA, FAMILIAL
Identifiers:
MONDO: MONDO:0011013; MedGen: C0342345; OMIM: 601198

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000761043Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 25, 2017) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Calcium-sensing receptor mutations and denaturing high performance liquid chromatography.

Cole DE, Yun FH, Wong BY, Shuen AY, Booth RA, Scillitani A, Pidasheva S, Zhou X, Canaff L, Hendy GN.

J Mol Endocrinol. 2009 Apr;42(4):331-9. doi: 10.1677/JME-08-0164. Epub 2009 Jan 29. Erratum in: J Mol Endocrinol. 2010 Apr;44(4):257.

PubMed [citation]
PMID:
19179454

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000761043.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces serine with glycine at codon 166 of the CASR protein (p.Ser166Gly). The serine residue is highly conserved and there is a small physicochemical difference between serine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with familial hypocalciuric hypercalcemia (PMID: 19179454). ClinVar contains an entry for this variant (Variation ID: 35800). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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: Apr 23, 2022