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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 5, 2017
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:: RCV000589097.1

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:: 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
SCV000695307	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jun 5, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22267502, 10338090 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000695307

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jun 5, 2017)

germline

clinical testing

PubMed (2)
[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

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

Cystathionine beta-synthase mutations in homocystinuria.

Kraus JP, Janosík M, Kozich V, Mandell R, Shih V, Sperandeo MP, Sebastio G, de Franchis R, Andria G, Kluijtmans LA, Blom H, Boers GH, Gordon RB, Kamoun P, Tsai MY, Kruger WD, Koch HG, Ohura T, Gaustadnes M.

Hum Mutat. 1999;13(5):362-75. Review.

PubMed [citation]

PMID:: 10338090

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000695307.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: The CBS c.572C>T (p.Thr191Met) variant involves the alteration of a conserved nucleotide, is located in dimer interface of the active core of the protein (Hnizda_2012) and is predicted to be damaging by 5/5 in silico tools. Multiple functional studies show that this variant causes severe impairment in protein structure and/or function (Kraus_1999, Kraus_2012, Mayfield_2012). This variant is absent in 117282 control chromosomes from ExAC. This variant is a known common pathogenic variant that causes homocystinuria. It is highly prevalent in homocystinuric patients from Spain, Portugal and South America. Genotype-phenotype correlation study show this variant leads to non-responsiveness to vitamin B6. One clinical laboratory and one reputable database (via ClinVar) have have classified this variant as pathogenic. Taken together, this variant is 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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