NM_000071.3(CBS):c.700G>A (p.Asp234Asn) AND HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 25, 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:: RCV002228832.12

Allele description [Variation Report for NM_000071.3(CBS):c.700G>A (p.Asp234Asn)]

NM_000071.3(CBS):c.700G>A (p.Asp234Asn)

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.700G>A (p.Asp234Asn)

Other names:

p.D234N:GAC>AAC

HGVS:

NC_000021.9:g.43065239C>T
NG_008938.1:g.15692G>A
NM_000071.3:c.700G>AMANE SELECT
NM_001178008.3:c.700G>A
NM_001178009.3:c.700G>A
NM_001320298.2:c.700G>A
NM_001321072.1:c.385G>A
NP_000062.1:p.Asp234Asn
NP_000062.1:p.Asp234Asn
NP_001171479.1:p.Asp234Asn
NP_001171480.1:p.Asp234Asn
NP_001307227.1:p.Asp234Asn
NP_001308001.1:p.Asp129Asn
LRG_777t1:c.700G>A
LRG_777:g.15692G>A
LRG_777p1:p.Asp234Asn
NC_000021.8:g.44485349C>T
NM_000071.2:c.700G>A
P35520:p.Asp234Asn

Protein change:

D129N

Links:

UniProtKB: P35520#VAR_008071; dbSNP: rs773734233

NCBI 1000 Genomes Browser:

rs773734233

Molecular consequence:

NM_000071.3:c.700G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001178008.3:c.700G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001178009.3:c.700G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001320298.2:c.700G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001321072.1:c.385G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
Identifiers:: MedGen: C3150344

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001385812	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 25, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 14972327, 16786517, 22267502, 23981774, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001385812

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 25, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Characterization of cystathionine beta-synthase gene mutations in homocystinuric Venezuelan patients: identification of one novel mutation in exon 6.

De Lucca M, Casique L.

Mol Genet Metab. 2004 Mar;81(3):209-15.

PubMed [citation]

PMID:: 14972327

A common mutation in the CBS gene explains a high incidence of homocystinuria in the Qatari population.

El-Said MF, Badii R, Bessisso MS, Shahbek N, El-Ali MG, El-Marikhie M, El-Zyoid M, Salem MS, Bener A, Hoffmann GF, Zschocke J.

Hum Mutat. 2006 Jul;27(7):719.

PubMed [citation]

PMID:: 16786517

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001385812.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 234 of the CBS protein (p.Asp234Asn). This variant is present in population databases (rs773734233, gnomAD 0.006%). This missense change has been observed in individual(s) with homocystinuria (PMID: 14972327, 16786517; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 212852). 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 expected to disrupt CBS protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CBS function (PMID: 22267502, 23981774). For these reasons, this variant has been 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: Sep 29, 2024

ClinVar

Relating variation to medicine