NM_000782.5(CYP24A1):c.1226T>C (p.Leu409Ser) AND Hypercalcemia, infantile, 1

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: Jul 8, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000033210.27

Allele description [Variation Report for NM_000782.5(CYP24A1):c.1226T>C (p.Leu409Ser)]

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

Gene:
CYP24A1:cytochrome P450 family 24 subfamily A member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20q13.2
Genomic location:
Preferred name:
NM_000782.5(CYP24A1):c.1226T>C (p.Leu409Ser)
Other names:
CYP24A1, LEU409SER (rs6068812)
HGVS:
  • NC_000020.11:g.54158096A>G
  • NG_008334.1:g.20882T>C
  • NM_000782.5:c.1226T>CMANE SELECT
  • NM_001128915.2:c.1226T>C
  • NP_000773.2:p.Leu409Ser
  • NP_001122387.1:p.Leu409Ser
  • NC_000020.10:g.52774635A>G
  • NM_000782.4:c.1226T>C
  • Q07973:p.Leu409Ser
Protein change:
L409S; LEU409SER
Links:
UniProtKB: Q07973#VAR_048466; OMIM: 126065.0006; dbSNP: rs6068812
NCBI 1000 Genomes Browser:
rs6068812
Molecular consequence:
  • NM_000782.5:c.1226T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128915.2:c.1226T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Hypercalcemia, infantile, 1 (HCINF1)
Identifiers:
MONDO: MONDO:0020739; MedGen: C4310232; Orphanet: 300547; OMIM: 143880

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000057056OMIMno assertion criteria providedPathogenic
(Nov 3, 2011)
germlineliterature only

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

SCV001300125Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Apr 27, 2017)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link,

SCV001448825Knight Diagnostic Laboratories, Oregon Health and Sciences Universitycriteria provided, single submitter
Likely pathogenic
(Jul 8, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineunknown1not providednot providednot providednot providedclinical testing

Citations

PubMed

CYP24A1 mutations in idiopathic infantile hypercalcemia.

Ji HF, Shen L.

N Engl J Med. 2011 Nov 3;365(18):1741; author reply 1742-3. doi: 10.1056/NEJMc1110226. No abstract available.

PubMed [citation]
PMID:
22047571

Kidney function and influence of sunlight exposure in patients with impaired 24-hydroxylation of vitamin D due to CYP24A1 mutations.

Figueres ML, Linglart A, Bienaime F, Allain-Launay E, Roussey-Kessler G, Ryckewaert A, Kottler ML, Hourmant M.

Am J Kidney Dis. 2015 Jan;65(1):122-6. doi: 10.1053/j.ajkd.2014.06.037. Epub 2014 Nov 4.

PubMed [citation]
PMID:
25446019
See all PubMed Citations (8)

Details of each submission

From OMIM, SCV000057056.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

For discussion of the leu409-to-ser (L409S) mutation in the CYP24A1 gene that was found in compound heterozygous state in 2 sibs with infantile hypercalcemia (HCINF1; 143880) by Schlingmann et al. (2011), see 126065.0005.

In molecular-modeling simulations, Ji and Shen (2011) found that the L409S mutation weakens the binding of 1,25-dihydroxyvitamin D3 to 24-hydroxylase.

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

From Illumina Clinical Services Laboratory,Illumina, SCV001300125.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

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, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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

From Knight Diagnostic Laboratories, Oregon Health and Sciences University, SCV001448825.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

Last Updated: Oct 8, 2021

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