NM_000071.3(CBS):c.572C>T (p.Thr191Met) AND HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 24, 2024
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:: RCV002227962.4

Allele description [Variation Report for NM_000071.3(CBS):c.572C>T (p.Thr191Met)]

NM_000071.3(CBS):c.572C>T (p.Thr191Met)

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.572C>T (p.Thr191Met)

Other names:

p.T191M:ACG>ATG

HGVS:

NC_000021.9:g.43065481G>A
NG_008938.1:g.15450C>T
NM_000071.3:c.572C>TMANE SELECT
NM_001178008.3:c.572C>T
NM_001178009.3:c.572C>T
NM_001320298.2:c.572C>T
NM_001321072.1:c.257C>T
NP_000062.1:p.Thr191Met
NP_000062.1:p.Thr191Met
NP_001171479.1:p.Thr191Met
NP_001171480.1:p.Thr191Met
NP_001307227.1:p.Thr191Met
NP_001308001.1:p.Thr86Met
LRG_777t1:c.572C>T
LRG_777:g.15450C>T
LRG_777p1:p.Thr191Met
NC_000021.8:g.44485591G>A
NM_000071.2:c.572C>T
P35520:p.Thr191Met

Protein change:

T191M; THR191MET

Links:

UniProtKB: P35520#VAR_008068; OMIM: 613381.0016; dbSNP: rs121964973

NCBI 1000 Genomes Browser:

rs121964973

Molecular consequence:

NM_000071.3:c.572C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001178008.3:c.572C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001178009.3:c.572C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001320298.2:c.572C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001321072.1:c.257C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000769933	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 24, 2024)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 12815602, 15993874, 16470595, 16479318, 25218699, 10338090, 16429402, 22069143, 22267502, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000769933

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 24, 2024)

germline

clinical testing

PubMed (10)
[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

Spectrum of CBS mutations in 16 homocystinuric patients from the Iberian Peninsula: high prevalence of T191M and absence of I278T or G307S.

Urreizti R, Balcells S, Rodés M, Vilarinho L, Baldellou A, Couce ML, Muñoz C, Campistol J, Pintó X, Vilaseca MA, Grinberg D.

Hum Mutat. 2003 Jul;22(1):103.

PubMed [citation]

PMID:: 12815602

Molecular analysis of homocystinuria in Brazilian patients.

Porto MP, Galdieri LC, Pereira VG, Vergani N, da Rocha JC, Micheletti C, Martins AM, Perez AB, Almeida VD.

Clin Chim Acta. 2005 Dec;362(1-2):71-8. Epub 2005 Jul 5.

PubMed [citation]

PMID:: 15993874

See all PubMed Citations (10)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000769933.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 191 of the CBS protein (p.Thr191Met). This variant is present in population databases (rs121964973, gnomAD 0.04%). This missense change has been observed in individual(s) with homocystinuria (PMID: 12815602, 15993874, 16470595, 16479318, 25218699). ClinVar contains an entry for this variant (Variation ID: 132). 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: 10338090, 16429402, 22069143, 22267502). 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: Nov 24, 2024

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