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NM_000071.3(CBS):c.325T>C (p.Cys109Arg)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Sep 24, 2021)
Last evaluated:
Sep 17, 2020
Accession:
VCV000212878.10
Variation ID:
212878
Description:
single nucleotide variant
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NM_000071.3(CBS):c.325T>C (p.Cys109Arg)

Allele ID
210444
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
21q22.3
Genomic location
21: 43066369 (GRCh38) GRCh38 UCSC
21: 44486479 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P35520:p.Cys109Arg
LRG_777:g.14562T>C
LRG_777t1:c.325T>C LRG_777p1:p.Cys109Arg
... more HGVS
Protein change
C109R, C4R
Other names
p.C109R:TGT>CGT
Canonical SPDI
NC_000021.9:43066368:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00002
The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00003
Links
ClinGen: CA324303
UniProtKB: P35520#VAR_021792
dbSNP: rs778220779
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, multiple submitters, no conflicts Apr 19, 2019 RCV000199752.3
Pathogenic 1 criteria provided, single submitter Aug 13, 2014 RCV000248928.1
Pathogenic 3 criteria provided, single submitter Sep 17, 2020 RCV000535881.8
Pathogenic 1 criteria provided, single submitter Jan 26, 2016 RCV000588375.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CBS - - GRCh38
GRCh37
708 789

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jan 26, 2016)
criteria provided, single submitter
Method: clinical testing
Homocystinuria
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695304.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (2)
Comment:
Variant summary: The c.325T>C in CBS gene is a missense variant that involves a highly conserved nucleotide and 5/5 in silico tools predict deleterious outcome. … (more)
Pathogenic
(May 02, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000700264.2
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (2)
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Aug 13, 2014)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000319354.5
Submitted: (Nov 30, 2020)
Evidence details
Pathogenic
(Sep 17, 2020)
criteria provided, single submitter
Method: clinical testing
Classic homocystinuria
Allele origin: germline
Invitae
Accession: SCV000649832.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces cysteine with arginine at codon 109 of the CBS protein (p.Cys109Arg). The cysteine residue is moderately conserved and there is a … (more)
Pathogenic
(Apr 19, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000249727.11
Submitted: (Sep 24, 2021)
Evidence details
Comment:
In a yeast system lacking the CBS ortholog, expression of a construct with C109R showed a failure to restore function /rescue growth (Gaustadnes, 2002; Mayfield … (more)
Likely pathogenic
(Jan 17, 2018)
no assertion criteria provided
Method: clinical testing
Classic homocystinuria
Allele origin: unknown
Counsyl
Accession: SCV000797245.2
Submitted: (Aug 05, 2019)
Evidence details
Publications
PubMed (4)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Homocystinuria due to cystathionine beta-synthase deficiency
Allele origin: germline
Natera, Inc.
Accession: SCV001452100.1
Submitted: (Dec 28, 2020)
Evidence details

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
Homocystinuria due to cystathionine beta-synthase (CBS) deficiency in Russia: Molecular and clinical characterization. Voskoboeva E Molecular genetics and metabolism reports 2017 PMID: 29326875
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Case 34-2016. A 17-Year-Old Boy with Myopia and Craniofacial and Skeletal Abnormalities. Sweetser DA The New England journal of medicine 2016 PMID: 27959664
Surrogate genetics and metabolic profiling for characterization of human disease alleles. Mayfield JA Genetics 2012 PMID: 22267502
The molecular basis of cystathionine beta-synthase deficiency in Australian patients: genotype-phenotype correlations and response to treatment. Gaustadnes M Human mutation 2002 PMID: 12124992
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CBS - - - -

Text-mined citations for rs778220779...

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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 Nov 27, 2021