VCV000060669.1 - ClinVar

NM_000388.4(CASR):c.85A>G (p.Lys29Glu)

Germline

Classification

no assertion criteria provided. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (1)

This classification is based on the single submission received

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000388.4(CASR):c.85A>G (p.Lys29Glu)

Variation ID: 60669 Accession: VCV000060669.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3q21.1 3: 122254274 (GRCh38) [ NCBI UCSC ] 3: 121973121 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 25, 2017	Feb 25, 2017	Jul 1, 2006

HGVS

Nucleotide	Protein	Molecular consequence
NM_000388.4:c.85A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000379.3:p.Lys29Glu	missense
NM_001178065.2:c.85A>G	NP_001171536.2:p.Lys29Glu	missense
NC_000003.12:g.122254274A>G
NC_000003.11:g.121973121A>G
NG_009058.1:g.75592A>G

... more HGVS ... less HGVS

Protein change

K29E

Other names

Canonical SPDI

NC_000003.12:122254273:A:G

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA144613 OMIM: 601199.0053 dbSNP: rs397514729 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CASR		No evidence available	No evidence available	GRCh38 GRCh37	3134	3159

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Bartter syndrome with hypocalcemia	Pathogenic (1)	no assertion criteria provided	Jul 1, 2006	RCV000054483.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jul 01, 2006) C Contributing to aggregate classification	no assertion criteria provided	HYPOCALCEMIA, AUTOSOMAL DOMINANT 1, WITH BARTTER SYNDROME	OMIM Accession: SCV000082960.3 First in ClinVar: Aug 23, 2013 Last updated: Feb 25, 2017	Publications: PubMed (2) PubMed: 15005845‚ 17048213 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: In monozygotic twin sisters of Italian origin who presented with severe hypocalcemia in the neonatal period (601198), Hu et al. (2004) identified heterozygosity for a … (more) In monozygotic twin sisters of Italian origin who presented with severe hypocalcemia in the neonatal period (601198), Hu et al. (2004) identified heterozygosity for a de novo c.85A-G transition in exon 2 of the CASR gene, resulting in a lys29-to-glu (K29E) substitution in the extracellular VFT domain. The mutation was not present in their unaffected parents or older sister. In transfected HEK293 cells, the mutant K29E calcium-sensing receptor showed a marked increase in Ca(2+) sensitivity, including when it was cotransfected with wildtype CASR cDNA, consistent with a dominant effect. In a follow-up study, Vezzoli et al. (2006) reported that the twins developed Bartter syndrome (see 601198)-like features at age 22 years, with mild hypokalemia, mild hyperreninemia and hyperaldosteronism, but no alkalosis. (less)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Autosomal dominant hypocalcemia with mild type 5 Bartter syndrome.	Vezzoli G	Journal of nephrology	2006	PMID: 17048213
Autosomal dominant hypocalcemia in monozygotic twins caused by a de novo germline mutation near the amino-terminus of the human calcium receptor.	Hu J	Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research	2004	PMID: 15005845

Text-mined citations for rs397514729 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Dec 27, 2025