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NM_000071.2(CBS):c.302T>C (p.Leu101Pro)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
3 (Most recent: Jan 7, 2021)
Last evaluated:
Aug 27, 2020
Accession:
VCV000189185.5
Variation ID:
189185
Description:
single nucleotide variant
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NM_000071.2(CBS):c.302T>C (p.Leu101Pro)

Allele ID
187062
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
21q22.3
Genomic location
21: 43068523 (GRCh38) GRCh38 UCSC
21: 44488633 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P35520:p.Leu101Pro
NC_000021.8:g.44488633A>G
NC_000021.9:g.43068523A>G
... more HGVS
Protein change
L101P
Other names
-
Canonical SPDI
NC_000021.9:43068522:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA274473
UniProtKB: P35520#VAR_021791
dbSNP: rs786204757
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Aug 27, 2020 RCV000169617.5
Pathogenic 1 criteria provided, single submitter Jul 20, 2020 RCV001251397.1
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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
698 -

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Feb 18, 2015)
criteria provided, single submitter
Method: literature only
Homocystinuria due to CBS deficiency
(Autosomal recessive inheritance)
Allele origin: unknown
Counsyl
Accession: SCV000221143.1
Submitted: (Mar 11, 2015)
Evidence details
Publications
PubMed (8)
Pathogenic
(Aug 27, 2020)
criteria provided, single submitter
Method: clinical testing
Classic homocystinuria
Allele origin: germline
Invitae
Accession: SCV000826966.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change replaces leucine with proline at codon 101 of the CBS protein (p.Leu101Pro). The leucine residue is moderately conserved and there is a … (more)
Pathogenic
(Jul 20, 2020)
criteria provided, single submitter
Method: clinical testing
Homocystinuria
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001426983.1
Submitted: (Aug 06, 2020)
Evidence details
Publications
PubMed (5)
Comment:
Variant summary: CBS c.302T>C (p.Leu101Pro) results in a non-conservative amino acid change located in the Pyridoxal-phosphate dependent enzyme domain (IPR001926) of the encoded protein sequence. … (more)

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
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
Surrogate genetics and metabolic profiling for characterization of human disease alleles. Mayfield JA Genetics 2012 PMID: 22267502
Testing computational prediction of missense mutation phenotypes: functional characterization of 204 mutations of human cystathionine beta synthase. Wei Q Proteins 2010 PMID: 20455263
Activation of mutant enzyme function in vivo by proteasome inhibitors and treatments that induce Hsp70. Singh LR PLoS genetics 2010 PMID: 20066033
Structural insights into pathogenic mutations in heme-dependent cystathionine-beta-synthase. Yamanishi M Journal of inorganic biochemistry 2006 PMID: 17069888
Cystathionine beta-synthase deficiency in Georgia (USA): correlation of clinical and biochemical phenotype with genotype. Kruger WD Human mutation 2003 PMID: 14635102
Structural insights into mutations of cystathionine beta-synthase. Meier M Biochimica et biophysica acta 2003 PMID: 12686134
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
Characterization of mutations in the cystathionine beta-synthase gene in Irish patients with homocystinuria. Gallagher PM Molecular genetics and metabolism 1998 PMID: 9889017

Text-mined citations for rs786204757...

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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 Oct 08, 2021