NM_000782.5(CYP24A1):c.1226T>C (p.Leu409Ser) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jul 1, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000785821.6

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:
5

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000924393Molecular Diagnostics Lab,Nemours Alfred I. duPont Hospital for Childrencriteria provided, single submitter
Likely pathogenic
(Oct 14, 2016)
unknownclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001209677Invitaecriteria provided, single submitter
Pathogenic
(Oct 19, 2020)
germlineclinical testing

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

SCV001246621CeGaT Praxis fuer Humangenetik Tuebingencriteria provided, single submitter
Pathogenic
(Jul 1, 2021)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyes4not providednot providednot providednot providedclinical testing
not providedunknownyes1not providednot provided1not 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753
See all PubMed Citations (8)

Details of each submission

From Molecular Diagnostics Lab,Nemours Alfred I. duPont Hospital for Children, SCV000924393.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

profound hypercalcemia in pregnanacy

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyes1not providednot provided1not providednot providednot provided

From Invitae, SCV001209677.2

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

Description

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 large physicochemical difference between leucine and serine. This variant is present in population databases (rs6068812, ExAC 0.1%). This variant has been reported as homozygous and compound heterozygous in multiple individuals with hypercalcemia and/or nephrolithiasis (PMID: 21675912, 26846157, 23470222, 26214117). ClinVar contains an entry for this variant (Variation ID: 29680). Experimental studies have shown that this missense change disrupts CYP24A1 enzyme activity (PMID: 21675912, 23423976). For these reasons, this variant has been classified as Pathogenic.

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

From CeGaT Praxis fuer Humangenetik Tuebingen, SCV001246621.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided4not providednot providednot provided

Last Updated: Oct 8, 2021

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