NM_000071.3(CBS):c.325T>C (p.Cys109Arg) AND not provided

Clinical significance:Pathogenic (Last evaluated: Apr 19, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000199752.3

Allele description [Variation Report for NM_000071.3(CBS):c.325T>C (p.Cys109Arg)]

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

Gene:
CBS:cystathionine beta-synthase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
21q22.3
Genomic location:
Preferred name:
NM_000071.3(CBS):c.325T>C (p.Cys109Arg)
Other names:
p.C109R:TGT>CGT
HGVS:
  • NC_000021.9:g.43066369A>G
  • NG_008938.1:g.14562T>C
  • NM_000071.2:c.325T>C
  • NM_000071.3:c.325T>CMANE SELECT
  • NM_001178008.3:c.325T>C
  • NM_001178009.3:c.325T>C
  • NM_001320298.2:c.325T>C
  • NM_001321072.1:c.10T>C
  • NP_000062.1:p.Cys109Arg
  • NP_000062.1:p.Cys109Arg
  • NP_001171479.1:p.Cys109Arg
  • NP_001171480.1:p.Cys109Arg
  • NP_001307227.1:p.Cys109Arg
  • NP_001308001.1:p.Cys4Arg
  • LRG_777t1:c.325T>C
  • LRG_777:g.14562T>C
  • LRG_777p1:p.Cys109Arg
  • NC_000021.8:g.44486479A>G
  • P35520:p.Cys109Arg
Protein change:
C109R
Links:
UniProtKB: P35520#VAR_021792; dbSNP: rs778220779
NCBI 1000 Genomes Browser:
rs778220779
Molecular consequence:
  • NM_000071.2:c.325T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000071.3:c.325T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178008.3:c.325T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178009.3:c.325T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320298.2:c.325T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001321072.1:c.10T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000249727GeneDxcriteria provided, single submitter
Pathogenic
(Apr 19, 2019)
germlineclinical testing

Citation Link,

SCV000700264EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(May 2, 2017)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown3not providednot providednot providednot providedclinical testing

Citations

PubMed

The molecular basis of cystathionine beta-synthase deficiency in Australian patients: genotype-phenotype correlations and response to treatment.

Gaustadnes M, Wilcken B, Oliveriusova J, McGill J, Fletcher J, Kraus JP, Wilcken DE.

Hum Mutat. 2002 Aug;20(2):117-26.

PubMed [citation]
PMID:
12124992

Surrogate genetics and metabolic profiling for characterization of human disease alleles.

Mayfield JA, Davies MW, Dimster-Denk D, Pleskac N, McCarthy S, Boydston EA, Fink L, Lin XX, Narain AS, Meighan M, Rine J.

Genetics. 2012 Apr;190(4):1309-23. doi: 10.1534/genetics.111.137471. Epub 2012 Jan 20. Erratum in: Genetics. 2012 Oct;192(2):759-60.

PubMed [citation]
PMID:
22267502
PMCID:
PMC3316645

Details of each submission

From GeneDx, SCV000249727.11

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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 et al., 2012); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27959664, 22267502, 12124992, 29326875)

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

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000700264.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

Last Updated: Nov 20, 2021

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