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NM_000784.4(CYP27A1):c.410G>A (p.Arg137Gln)

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Interpretation:
Conflicting interpretations of pathogenicity​

Pathogenic(3);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Feb 26, 2021)
Last evaluated:
Feb 2, 2021
Accession:
VCV000065929.7
Variation ID:
65929
Description:
single nucleotide variant
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NM_000784.4(CYP27A1):c.410G>A (p.Arg137Gln)

Allele ID
76837
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2q35
Genomic location
2: 218809731 (GRCh38) GRCh38 UCSC
2: 219674454 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.11:g.219674454G>A
NC_000002.12:g.218809731G>A
NG_007959.1:g.32983G>A
NM_000784.4:c.410G>A MANE Select NP_000775.1:p.Arg137Gln missense
Protein change
R137Q
Other names
-
Canonical SPDI
NC_000002.12:218809730:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD) 0.00006
The Genome Aggregation Database (gnomAD), exomes 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00006
Links
ClinGen: CA345260
dbSNP: rs587778818
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Oct 23, 2020 RCV001267947.1
Conflicting interpretations of pathogenicity 4 criteria provided, conflicting interpretations Feb 2, 2021 RCV000056176.6
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CYP27A1 - - GRCh38
GRCh37
416 439

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Mar 30, 2017)
criteria provided, single submitter
Method: clinical testing
Cholestanol storage disease
Allele origin: unknown
Counsyl
Accession: SCV000800509.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (1)
Pathogenic
(Oct 23, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
(Unknown mechanism)
Allele origin: germline
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446469.1
Submitted: (Oct 23, 2020)
Evidence details
Pathogenic
(Feb 02, 2021)
criteria provided, single submitter
Method: clinical testing
Cholestanol storage disease
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001482211.1
Submitted: (Feb 26, 2021)
Evidence details
Publications
PubMed (4)
Comment:
Variant summary: CYP27A1 c.410G>A (p.Arg137Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging … (more)
Pathogenic
(Oct 09, 2020)
criteria provided, single submitter
Method: clinical testing
Cholestanol storage disease
Allele origin: germline
Invitae
Accession: SCV000960176.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces arginine with glutamine at codon 137 of the CYP27A1 protein (p.Arg137Gln). The arginine residue is highly conserved and there is a … (more)
pathologic
(Aug 01, 2013)
no assertion criteria provided
Method: curation
Cerebrotendinous Xanthomatosis
Allele origin: not provided
GeneReviews
Accession: SCV000087264.1
Submitted: (Apr 30, 2013)
Evidence details
Comment:
Converted during submission to Pathogenic.

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
Molecular findings in children with inherited intrahepatic cholestasis. Wang NL Pediatric research 2020 PMID: 31450232
Clinical and genetic characteristics of Chinese patients with cerebrotendinous xanthomatosis. Tao QQ Orphanet journal of rare diseases 2019 PMID: 31796091
Prominent Tendon Xanthomas and Abdominal Aortic Aneurysm Associated with Cerebrotendinous Xanthomatosis Identified Using Whole Exome Sequencing. Tada H Internal medicine (Tokyo, Japan) 2018 PMID: 29269672
Clinical and molecular genetic features of cerebrotendinous xanthomatosis patients in Chinese families. Chen C Metabolic brain disease 2017 PMID: 28623566
Cerebrotendinous Xanthomatosis Federico A - 2016 PMID: 20301583
Identification of a novel missense mutation in the sterol 27-hydroxylase gene in two Japanese patients with cerebrotendinous xanthomatosis. Nozue T Internal medicine (Tokyo, Japan) 2010 PMID: 20558929
Mutational analysis of CYP27A1: assessment of 27-hydroxylation of cholesterol and 25-hydroxylation of vitamin D. Gupta RP Metabolism: clinical and experimental 2007 PMID: 17697869
A point mutation in the bile acid biosynthetic enzyme sterol 27-hydroxylase in a family with cerebrotendinous xanthomatosis. Nakashima N Journal of lipid research 1994 PMID: 8006521

Text-mined citations for rs587778818...

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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 Sep 29, 2021