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NM_000782.5(CYP24A1):c.1226T>C (p.Leu409Ser)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(2);Pathogenic(2);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Jul 4, 2021)
Last evaluated:
Jul 1, 2021
Accession:
VCV000029680.13
Variation ID:
29680
Description:
single nucleotide variant
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NM_000782.5(CYP24A1):c.1226T>C (p.Leu409Ser)

Allele ID
38635
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
20q13.2
Genomic location
20: 54158096 (GRCh38) GRCh38 UCSC
20: 52774635 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
Q07973:p.Leu409Ser
NC_000020.10:g.52774635A>G
NC_000020.11:g.54158096A>G
... more HGVS
Protein change
L409S
Other names
CYP24A1, LEU409SER (rs6068812)
Canonical SPDI
NC_000020.11:54158095:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (G)

Allele frequency
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD) 0.00067
The Genome Aggregation Database (gnomAD), exomes 0.00075
Trans-Omics for Precision Medicine (TOPMed) 0.00094
Exome Aggregation Consortium (ExAC) 0.00071
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00131
Links
ClinGen: CA130776
UniProtKB: Q07973#VAR_048466
OMIM: 126065.0006
dbSNP: rs6068812
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 3 criteria provided, multiple submitters, no conflicts Jul 1, 2021 RCV000785821.6
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Jul 8, 2019 RCV000033210.27

Clinical features observed in individuals with this variant

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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CYP24A1 - - GRCh38
GRCh37
189 200

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Oct 14, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: unknown
Molecular Diagnostics Lab,Nemours Alfred I. duPont Hospital for Children
Accession: SCV000924393.1
Submitted: (Jan 20, 2017)
Evidence details
Publications
PubMed (2)
Uncertain significance
(Apr 27, 2017)
criteria provided, single submitter
Method: clinical testing
Hypercalcemia, infantile, 1
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001300125.1
Submitted: (Feb 20, 2020)
Evidence details
Publications
PubMed (6)
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Likely pathogenic
(Jul 08, 2019)
criteria provided, single submitter
Method: clinical testing
Hypercalcemia, infantile, 1
Allele origin: germline
Knight Diagnostic Laboratories, Oregon Health and Sciences University
Accession: SCV001448825.1
Submitted: (Sep 02, 2020)
Evidence details
Pathogenic
(Oct 19, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Invitae
Accession: SCV001209677.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces leucine with serine at codon 409 of the CYP24A1 protein (p.Leu409Ser). The leucine residue is moderately conserved and there is a … (more)
Pathogenic
(Jul 01, 2021)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001246621.6
Submitted: (Jul 04, 2021)
Evidence details
Pathogenic
(Nov 03, 2011)
no assertion criteria provided
Method: literature only
HYPERCALCEMIA, INFANTILE, 1
Allele origin: germline
OMIM
Accession: SCV000057056.3
Submitted: (Nov 09, 2011)
Evidence details
Publications
PubMed (2)

Functional evidence

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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.

Citations for this variant

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Title Author Journal Year Link
The NIH Undiagnosed Diseases Program and Network: Applications to modern medicine. Gahl WA Molecular genetics and metabolism 2016 PMID: 26846157
CYP24A1 Mutations in a Cohort of Hypercalcemic Patients: Evidence for a Recessive Trait. Molin A The Journal of clinical endocrinology and metabolism 2015 PMID: 26214117
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
Quantitation of CYP24A1 enzymatic activity with a simple two-hybrid system. Mugg A The Journal of clinical endocrinology and metabolism 2015 PMID: 25375986
Loss-of-function mutations of CYP24A1, the vitamin D 24-hydroxylase gene, cause long-standing hypercalciuric nephrolithiasis and nephrocalcinosis. Dinour D The Journal of urology 2013 PMID: 23470222
CYP24A1 and CYP27B1 polymorphisms modulate vitamin D metabolism in colon cancer cells. Jacobs ET Cancer research 2013 PMID: 23423976
1,25-(OH)2D-24 Hydroxylase (CYP24A1) Deficiency as a Cause of Nephrolithiasis. Nesterova G Clinical journal of the American Society of Nephrology : CJASN 2013 PMID: 23293122
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

Text-mined citations for rs6068812...

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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 08, 2021