NM_000071.3(CBS):c.341C>T (p.Ala114Val) AND Homocystinuria

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 26, 2016
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:: RCV000590659.3

Allele description [Variation Report for NM_000071.3(CBS):c.341C>T (p.Ala114Val)]

NM_000071.3(CBS):c.341C>T (p.Ala114Val)

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.341C>T (p.Ala114Val)

Other names:

p.A114V:GCG>GTG

HGVS:

NC_000021.9:g.43066353G>A
NG_008938.1:g.14578C>T
NM_000071.3:c.341C>TMANE SELECT
NM_001178008.3:c.341C>T
NM_001178009.3:c.341C>T
NM_001320298.2:c.341C>T
NM_001321072.1:c.26C>T
NP_000062.1:p.Ala114Val
NP_000062.1:p.Ala114Val
NP_001171479.1:p.Ala114Val
NP_001171480.1:p.Ala114Val
NP_001307227.1:p.Ala114Val
NP_001308001.1:p.Ala9Val
LRG_777t1:c.341C>T
LRG_777:g.14578C>T
LRG_777p1:p.Ala114Val
NC_000021.8:g.44486463G>A
NM_000071.2:c.341C>T
P35520:p.Ala114Val

Protein change:

A114V; ALA114VAL

Links:

UniProtKB: P35520#VAR_002174; OMIM: 613381.0003; dbSNP: rs121964964

NCBI 1000 Genomes Browser:

rs121964964

Molecular consequence:

NM_000071.3:c.341C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001178008.3:c.341C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001178009.3:c.341C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001320298.2:c.341C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001321072.1:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Homocystinuria
Identifiers:: MONDO: MONDO:0004737; MedGen: C0019880; Human Phenotype Ontology: HP:0002156

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000695305	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jan 26, 2016)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 20506325, 8353501, 20490928, 22267502, 22612060, 14722927 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000695305

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jan 26, 2016)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Cystathionine beta-synthase mutations: effect of mutation topology on folding and activity.

Kozich V, Sokolová J, Klatovská V, Krijt J, Janosík M, Jelínek K, Kraus JP.

Hum Mutat. 2010 Jul;31(7):809-19. doi: 10.1002/humu.21273.

PubMed [citation]

PMID:: 20506325
PMCID:: PMC2966864

Molecular defect in a patient with pyridoxine-responsive homocystinuria.

Kozich V, de Franchis R, Kraus JP.

Hum Mol Genet. 1993 Jun;2(6):815-6. No abstract available.

PubMed [citation]

PMID:: 8353501

See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000695305.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Variant summary: The c.341C>T in CBS gene is a missense variant that involves a highly conserved nucleotide and 4/5 in silico tools predict deleterious outcome. The variant was observed in the large and broad cohorts of the ExAC ans ESP projects at an allele frequency of 0.027%. This frequency does not exceed the maximal expected allele frequency for a pathogenic variant in CBS (0.3%).suggesting this variant is not a common polymorphism. The variant has been reported in several affected individuals presented with features suggestive of Cystathionine--synthase deficiency. Functional studies performed in bacteria-based system showed slight misfolding of the recombinant protein and low enzymatic activity. The variant of interest has been reported as Pathogenic by several reputable databases/diagnostic centers.Taking together, the variant was classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 17, 2024

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