U.S. flag

An official website of the United States government

NM_000784.4(CYP27A1):c.1075G>C (p.Glu359Gln) AND Cholestanol storage disease

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 9, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003502583.2

Allele description [Variation Report for NM_000784.4(CYP27A1):c.1075G>C (p.Glu359Gln)]

NM_000784.4(CYP27A1):c.1075G>C (p.Glu359Gln)

Gene:
CYP27A1:cytochrome P450 family 27 subfamily A member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_000784.4(CYP27A1):c.1075G>C (p.Glu359Gln)
HGVS:
  • NC_000002.12:g.218814078G>C
  • NG_007959.1:g.37330G>C
  • NM_000784.4:c.1075G>CMANE SELECT
  • NP_000775.1:p.Glu359Gln
  • NC_000002.11:g.219678801G>C
  • NC_000002.11:g.219678801G>C
  • NM_000784.3:c.1075G>C
Protein change:
E359Q
Links:
dbSNP: rs760471205
NCBI 1000 Genomes Browser:
rs760471205
Molecular consequence:
  • NM_000784.4:c.1075G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cholestanol storage disease (CTX)
Synonyms:
Cerebral cholesterinosis; CTX: Cerebrotendinous xanthomatosis; Cerebrotendinous Xanthomatosis
Identifiers:
MONDO: MONDO:0008948; MedGen: C0238052; Orphanet: 909; OMIM: 213700

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004272297Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 9, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004272297.1

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

Description

This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 359 of the CYP27A1 protein (p.Glu359Gln). This variant is present in population databases (rs760471205, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CYP27A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 809161). 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) performed at Invitae indicates that this missense variant is not expected to disrupt CYP27A1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 20, 2024