VCV000029679.41 - ClinVar

NM_000782.5(CYP24A1):c.1186C>T (p.Arg396Trp)

Germline

Classification

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.

(16)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000782.5(CYP24A1):c.1186C>T (p.Arg396Trp)

Variation ID: 29679 Accession: VCV000029679.41

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 20q13.2 20: 54158136 (GRCh38) [ NCBI UCSC ] 20: 52774675 (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	Jul 5, 2015	Oct 20, 2024	May 29, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000782.5:c.1186C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000773.2:p.Arg396Trp	missense
NM_001128915.2:c.1186C>T	NP_001122387.1:p.Arg396Trp	missense
NC_000020.11:g.54158136G>A
NC_000020.10:g.52774675G>A
NG_008334.1:g.20842C>T
	Q07973:p.Arg396Trp

... more HGVS ... less HGVS

Protein change

R396W

Other names

CYP24A1, ARG396TRP (rs114368325)

Canonical SPDI

NC_000020.11:54158135:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

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.

0.00040 (A)

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

1000 Genomes Project 0.00040

1000 Genomes Project 30x 0.00047

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00054

Trans-Omics for Precision Medicine (TOPMed) 0.00064

The Genome Aggregation Database (gnomAD) 0.00079

Links

ClinGen: CA128554 UniProtKB: Q07973#VAR_066411 OMIM: 126065.0005 dbSNP: rs114368325 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.
CYP24A1		-	-	GRCh38 GRCh37	317	329

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.
Hypercalcemia, infantile, 1	Pathogenic/Likely pathogenic (9)	criteria provided, multiple submitters, no conflicts	Mar 20, 2024	RCV000022528.47
Muscle spasm	Pathogenic (1)	criteria provided, single submitter	Jul 1, 2015	RCV000414890.3
not provided	Pathogenic (6)	criteria provided, multiple submitters, no conflicts	May 29, 2024	RCV000731000.29

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.	More information 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, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Muscle spasm Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV000492784.1 First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017
Pathogenic (Dec 20, 2017)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000858770.1 First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP24A1 Number of individuals with the variant: 3 Sex: mixed
Pathogenic (Oct 20, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019) Method: clinical testing	Hypercalcemia, infantile, 1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000914961.1 First in ClinVar: May 24, 2019 Last updated: May 24, 2019	Publications: PubMed (7) PubMed: 23001465‚ 21675912‚ 25194629‚ 25446019‚ 26097993‚ 23485543‚ 26117226 Comment: The CYP24A1 c.1186C>T (p.Arg396Trp) variant has been reported in seven studies and identified in a total of ten individuals with infantile hypercalcemia including three homozygotes … (more) The CYP24A1 c.1186C>T (p.Arg396Trp) variant has been reported in seven studies and identified in a total of ten individuals with infantile hypercalcemia including three homozygotes and seven compound heterozygotes, two of which are siblings (Schlingmann et al. 2011; Fencl et al. 2013; Skalova et al. 2013; Dinour et al. 2015; Cools et al. 2015; Shah et al. 2015; Figueres et al. 2015). The p.Arg396Trp variant was identified in four of 1024 control alleles and is reported at a frequency of 0.001482 in the European (Finnish) population of the Genome Aggregation Database. Schlingmann et al. (2011) performed functional studies using transiently transfected V79-4 cells and observed a complete loss of enzyme activity in cells with the variant protein as compared to wild type. Based on the collective evidence, the p.Arg396Trp variant is classified as pathogenic for infantile hypercalcemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
Likely pathogenic (Sep 21, 2022)	criteria provided, single submitter (Classification criteria August 2017) Method: clinical testing	Hypercalcemia, infantile, 1 (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München Accession: SCV004045920.1 First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023	Number of individuals with the variant: 1 Clinical Features: Kidney disorder (present) , Abnormality of complement system (present) , Status post organ transplantation (present)
Pathogenic (Feb 17, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hypercalcemia, infantile, 1 Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV002018117.3 First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024
Pathogenic (Jan 22, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000952578.6 First in ClinVar: Aug 14, 2019 Last updated: Feb 20, 2024	Publications: PubMed (7) PubMed: 21675912‚ 23001465‚ 23485543‚ 25446019‚ 27394135‚ 27798933‚ 28470390 Comment: This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 396 of the CYP24A1 protein … (more) This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 396 of the CYP24A1 protein (p.Arg396Trp). This variant is present in population databases (rs114368325, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individuals with idiopathic infantile hypercalcemia (PMID: 21675912, 23001465, 23485543, 25446019, 27394135, 27798933, 28470390). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 29679). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CYP24A1 protein function. Experimental studies have shown that this missense change affects CYP24A1 function (PMID: 21675912). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Mar 20, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hypercalcemia, infantile, 1 Affected status: yes Allele origin: germline	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center Accession: SCV005043935.1 First in ClinVar: May 19, 2024 Last updated: May 19, 2024	Comment: PS3, PM3_Strong, PM5, PP3
Pathogenic (Feb 07, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics Laboratory, Skane University Hospital Lund Accession: SCV005197686.1 First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024
Pathogenic (May 29, 2024)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001818896.5 First in ClinVar: Sep 08, 2021 Last updated: Sep 16, 2024	Comment: Published functional studies demonstrate this variant results in the loss of enzymatic activity (PMID: 21675912); In silico analysis supports that this missense variant has a … (more) Published functional studies demonstrate this variant results in the loss of enzymatic activity (PMID: 21675912); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26097993, 36703897, 37701149, 23485543, 34337279, 34805638, 34320495, 34515170, 32743688, 23001465, 24518185, 22047571, 25194629, 21675912, 26117226, 28324001, 30729229, 29786188, 27798933, 31751313, 3490596, 25446019, 27394135, 31672324, 31980526, 26585929, 34307984, 34426522, 31589614, 33099630, 33186763, 33226606, 33502802, 33726816, 35569070, 28470390) (less)
Pathogenic (Oct 17, 2014)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown, yes Allele origin: unknown, biparental	Molecular Diagnostics Lab, Nemours Children's Health, Delaware Accession: SCV000924390.1 First in ClinVar: Jun 22, 2019 Last updated: Jun 22, 2019	Publications: PubMed (2) PubMed: 21675912‚ 22047571 Observation 1: Number of individuals with the variant: 1 Clinical Features: disorder of calcium metabolism (present) , nephrocalcinosis (present) Age: 20-29 years Sex: female Observation 2: Number of individuals with the variant: 1 Age: 0-9 years Sex: male Comment on evidence: incidental finding of hypercalcemia; co-occuring with c.427_429delGAA Observation 3: Number of individuals with the variant: 1 Age: 0-9 years Sex: female Comment on evidence: incidental finding of hypercalcemia co-occuring with c.427_429delGAA Observation 4: Number of individuals with the variant: 1 Age: 40-49 years Sex: female Observation 5: Age: 20-29 years Sex: female Comment on evidence: calcitrol-induced hypercalcemia, low 24,25 dihydroxy vitamin D, no hypercalcemia in family Observation 6: Number of individuals with the variant: 1 Age: 0-9 years Sex: male Comment on evidence: hypercalcemia
Pathogenic (May 23, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hypercalcemia, infantile, 1 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV000894223.2 First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022	Publications: PubMed (1) PubMed: 25741868 pmc: 4544753 pmc: 4544753 DOI: 10.1038/gim.2015.30 DOI: 10.1038/gim.2015.30
Pathogenic (Jan 05, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hypercalcemia, infantile, 1 (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Molecular Genetics, Royal Melbourne Hospital Additional submitter: Shariant Australia, Australian Genomics Accession: SCV004812447.1 First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024	Publications: PubMed (7) PubMed: 21675912‚ 23001465‚ 24518185‚ 34858904‚ 35956396‚ 36703897‚ 37701149 Comment: This sequence change in CYP24A1 is predicted to replace arginine with tryptophan at codon 396, p.(Arg396Trp). The arginine residue is highly conserved (100 vertebrates, UCSC). … (more) This sequence change in CYP24A1 is predicted to replace arginine with tryptophan at codon 396, p.(Arg396Trp). The arginine residue is highly conserved (100 vertebrates, UCSC). There is a large physicochemical difference between arginine and tryptophan. The highest population minor allele frequency in the population database gnomAD v2.1 is 0.1% (148/129,106 alleles) in the European non-Finnish population. This variant has been reported in multiple individuals with idiopathic infantile hypercalcaemia in the homozygous or compound heterozygous state (PMID: 21675912, 24518185, 23001465, 36703897, 34858904, 37701149). An in vitro functional assay with limited validation demonstrated the variant leads to a complete loss of enzyme activity (PMID: 21675912). A knock-in mouse model for the variant demonstrated a decrease in vitamin D levels and an increase in calcium levels indicating that this variant impacts protein function due to its reduced enzyme activity (PMID: 21675912, 35956396). Computational evidence predicts a deleterious effect for the missense substitution (REVEL = 0.873). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PM3_VeryStrong, PP3, PS3_Moderate (less)
Pathogenic (Jan 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004699454.8 First in ClinVar: Mar 10, 2024 Last updated: Oct 20, 2024	Comment: CYP24A1: PM3:Very Strong, PM5, PM2:Supporting Number of individuals with the variant: 1
Pathogenic (Nov 03, 2011)	no assertion criteria provided Method: literature only	HYPERCALCEMIA, INFANTILE, 1 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000043817.2 First in ClinVar: Apr 04, 2013 Last updated: May 29, 2016	Publications: PubMed (3) PubMed: 21675912‚ 3490596‚ 22047571 Comment on evidence: In a German patient who developed infantile hypercalcemia (HCINF1; 143880) following a 600,000 IU oral dose of vitamin D, Schlingmann et al. (2011) identified homozygosity … (more) In a German patient who developed infantile hypercalcemia (HCINF1; 143880) following a 600,000 IU oral dose of vitamin D, Schlingmann et al. (2011) identified homozygosity for a 1186C-T transition in the CYP24A1 gene, resulting in an arg396-to-trp (R396W) substitution. In 2 Russian brothers who developed infantile hypercalcemia while taking 500 IU of vitamin D per day, the R396W mutation was found in compound heterozygosity with a 1226T-C transition in the CYP24A1 gene, resulting in a leu409-to-ser (L409S; 126065.0006) substitution; and in 2 unrelated patients from Germany who developed hypercalcemia of infancy after 2 and 3 oral boluses of 600,000 IU of vitamin D, respectively, previously reported by Misselwitz and Hesse (1986), Schlingmann et al. (2011) identified compound heterozygosity for the R396W mutation and a 964G-A transition in CYP24A1, resulting in a glu322-to-lys (E322K; 126065.0007) substitution. The E322K mutation was not found in at least 204 control alleles; the R396W and L409S mutations, which had previously been annotated as putative polymorphisms in the dbSNP database, were tested in a sample of 1,024 control alleles, and L409S was not detected, but R396W was identified in 4 of the control alleles. Transfection studies demonstrated that R396W and E322K mutations resulted in complete loss of CYP24A1 catabolic activity, whereas the L409S mutation retained small but measurable levels of activity. In molecular-modeling simulations, Ji and Shen (2011) found that the R396W mutation changes interactions between the heme molecule and 24-hydroxylase, due to destruction of hydrogen bonds between the heme propionate group and arginine. (less)
Pathogenic (May 05, 2015)	no assertion criteria provided Method: research	Hypercalcemia, infantile Affected status: no Allele origin: germline	Division of Human Genetics, Children's Hospital of Philadelphia Study: CSER-PediSeq Accession: SCV000238444.1 First in ClinVar: Jul 05, 2015 Last updated: Jul 05, 2015	Publications: PubMed (3) PubMed: 21675912‚ 23001465‚ 24518185 Comment: This patient is a carrier of a heterozygous pathogenic variant in the CYP24A1 gene implicated in causing autosomal recessive infantile hypercalcemia (MIM 143880). The CYP24A1 … (more) This patient is a carrier of a heterozygous pathogenic variant in the CYP24A1 gene implicated in causing autosomal recessive infantile hypercalcemia (MIM 143880). The CYP24A1 variant (c.1186C>T) was identified in several patients in both the homozygous and compound heterozygous state (Schlingmann et al. 2011, PMID: 21675912; Fencl et al. 2013, PMID: 23001465; Wolf et al. 2014, PMID: 24518185). Functional studies of this variant showed an inability of the protein to metabolize 1,25-dihydroxyvitamin D3 (Schlingmann et al. 2011, PMID: 21675912). (less)
Pathogenic (Mar 08, 2024)	no assertion criteria provided Method: clinical testing	Hypercalcemia, infantile, 1 Affected status: yes Allele origin: maternal	Molecular Genetics Laboratory, Biocruces Bizkaia Health Research Institute Accession: SCV004708187.1 First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024
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Comment:

The CYP24A1 c.1186C>T (p.Arg396Trp) variant has been reported in seven studies and identified in a total of ten individuals with infantile hypercalcemia including three homozygotes and seven compound heterozygotes, two of which are siblings (Schlingmann et al. 2011; Fencl et al. 2013; Skalova et al. 2013; Dinour et al. 2015; Cools et al. 2015; Shah et al. 2015; Figueres et al. 2015). The p.Arg396Trp variant was identified in four of 1024 control alleles and is reported at a frequency of 0.001482 in the European (Finnish) population of the Genome Aggregation Database. Schlingmann et al. (2011) performed functional studies using transiently transfected V79-4 cells and observed a complete loss of enzyme activity in cells with the variant protein as compared to wild type. Based on the collective evidence, the p.Arg396Trp variant is classified as pathogenic for infantile hypercalcemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

Comment:

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 396 of the CYP24A1 protein (p.Arg396Trp). This variant is present in population databases (rs114368325, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individuals with idiopathic infantile hypercalcemia (PMID: 21675912, 23001465, 23485543, 25446019, 27394135, 27798933, 28470390). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 29679). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CYP24A1 protein function. Experimental studies have shown that this missense change affects CYP24A1 function (PMID: 21675912). For these reasons, this variant has been classified as Pathogenic.

Comment:

Published functional studies demonstrate this variant results in the loss of enzymatic activity (PMID: 21675912); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26097993, 36703897, 37701149, 23485543, 34337279, 34805638, 34320495, 34515170, 32743688, 23001465, 24518185, 22047571, 25194629, 21675912, 26117226, 28324001, 30729229, 29786188, 27798933, 31751313, 3490596, 25446019, 27394135, 31672324, 31980526, 26585929, 34307984, 34426522, 31589614, 33099630, 33186763, 33226606, 33502802, 33726816, 35569070, 28470390)

Comment:

This sequence change in CYP24A1 is predicted to replace arginine with tryptophan at codon 396, p.(Arg396Trp). The arginine residue is highly conserved (100 vertebrates, UCSC). There is a large physicochemical difference between arginine and tryptophan. The highest population minor allele frequency in the population database gnomAD v2.1 is 0.1% (148/129,106 alleles) in the European non-Finnish population. This variant has been reported in multiple individuals with idiopathic infantile hypercalcaemia in the homozygous or compound heterozygous state (PMID: 21675912, 24518185, 23001465, 36703897, 34858904, 37701149). An in vitro functional assay with limited validation demonstrated the variant leads to a complete loss of enzyme activity (PMID: 21675912). A knock-in mouse model for the variant demonstrated a decrease in vitamin D levels and an increase in calcium levels indicating that this variant impacts protein function due to its reduced enzyme activity (PMID: 21675912, 35956396). Computational evidence predicts a deleterious effect for the missense substitution (REVEL = 0.873). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PM3_VeryStrong, PP3, PS3_Moderate

Comment:

This patient is a carrier of a heterozygous pathogenic variant in the CYP24A1 gene implicated in causing autosomal recessive infantile hypercalcemia (MIM 143880). The CYP24A1 variant (c.1186C>T) was identified in several patients in both the homozygous and compound heterozygous state (Schlingmann et al. 2011, PMID: 21675912; Fencl et al. 2013, PMID: 23001465; Wolf et al. 2014, PMID: 24518185). Functional studies of this variant showed an inability of the protein to metabolize 1,25-dihydroxyvitamin D3 (Schlingmann et al. 2011, PMID: 21675912).

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Hypervitaminosis D Secondary to a CYP24A1 Loss-of-Function Mutation: An Unusual Cause of Hypercalcemia in Two Siblings.	Collins L	JBMR plus	2023	PMID: 37701149
Case report: Two heterozygous pathogenic variants of CYP24A1: A novel cause of hypercalcemia and nephrocalcinosis in adulthood.	Brunerova L	Frontiers in medicine	2023	PMID: 36703897
Vitamin D and Diseases of Mineral Homeostasis: A Cyp24a1 R396W Humanized Preclinical Model of Infantile Hypercalcemia Type 1.	St-Arnaud R	Nutrients	2022	PMID: 35956396
Childhood Hypercalciuric Hypercalcemia With Elevated Vitamin D and Suppressed Parathyroid Hormone: Long-Term Follow Up.	Gurevich E	Frontiers in pediatrics	2021	PMID: 34858904
Biallelic mutations in CYP24A1 or SLC34A1 as a cause of infantile idiopathic hypercalcemia (IIH) with vitamin D hypersensitivity: molecular study of 11 historical IIH cases.	Pronicka E	Journal of applied genetics	2017	PMID: 28470390
A Pediatric Patient with a CYP24A1 Mutation: Four Years of Clinical, Biochemical, and Imaging Follow-Up.	Ertl DA	Hormone research in paediatrics	2017	PMID: 27798933
Mutational Spectrum of CYP24A1 Gene in a Cohort of Italian Patients with Idiopathic Infantile Hypercalcemia.	Gigante M	Nephron	2016	PMID: 27394135
Calcium and bone homeostasis in heterozygous carriers of CYP24A1 mutations: A cross-sectional study.	Cools M	Bone	2015	PMID: 26117226
Maternal Hypercalcemia Due to Failure of 1,25-Dihydroxyvitamin-D3 Catabolism in a Patient With CYP24A1 Mutations.	Shah AD	The Journal of clinical endocrinology and metabolism	2015	PMID: 26097993
Kidney function and influence of sunlight exposure in patients with impaired 24-hydroxylation of vitamin D due to CYP24A1 mutations.	Figueres ML	American journal of kidney diseases : the official journal of the National Kidney Foundation	2015	PMID: 25446019
Maternal and infantile hypercalcemia caused by vitamin-D-hydroxylase mutations and vitamin D intake.	Dinour D	Pediatric nephrology (Berlin, Germany)	2015	PMID: 25194629
A Case of "Late-Onset" Idiopathic Infantile Hypercalcemia Secondary to Mutations in the CYP24A1 Gene.	Wolf P	Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists	2014	PMID: 24518185
Intravenous pamidronate in the treatment of severe idiopathic infantile hypercalcemia.	Skalova S	Iranian journal of kidney diseases	2013	PMID: 23485543
Severe hypercalcemic crisis in an infant with idiopathic infantile hypercalcemia caused by mutation in CYP24A1 gene.	Fencl F	European journal of pediatrics	2013	PMID: 23001465
CYP24A1 mutations in idiopathic infantile hypercalcemia.	Ji HF	The New England journal of medicine	2011	PMID: 22047571
Mutations in CYP24A1 and idiopathic infantile hypercalcemia.	Schlingmann KP	The New England journal of medicine	2011	PMID: 21675912
[Hypercalcemia following prophylactic vitamin D administration].	Misselwitz J	Kinderarztliche Praxis	1986	PMID: 3490596
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP24A1	-	-	-	-
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Text-mined citations for rs114368325 ...

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 Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_000782.5(CYP24A1):c.1186C>T (p.Arg396Trp)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs114368325 ...