NM_000071.3(CBS):c.1549del (p.Gln517fs) AND HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 15, 2022
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:: RCV003044032.3

Allele description [Variation Report for NM_000071.3(CBS):c.1549del (p.Gln517fs)]

NM_000071.3(CBS):c.1549del (p.Gln517fs)

Gene:

CBS:cystathionine beta-synthase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

21q22.3

Genomic location:

Preferred name:

NM_000071.3(CBS):c.1549del (p.Gln517fs)

HGVS:

NC_000021.9:g.43056807del
NG_008938.1:g.24125del
NM_000071.3:c.1549delMANE SELECT
NM_001178008.3:c.1549del
NM_001178009.3:c.1549del
NM_001320298.2:c.1549del
NM_001321072.1:c.1234del
NP_000062.1:p.Gln517Serfs
NP_000062.1:p.Gln517fs
NP_001171479.1:p.Gln517fs
NP_001171480.1:p.Gln517fs
NP_001307227.1:p.Gln517fs
NP_001308001.1:p.Gln412fs
LRG_777t1:c.1548del
LRG_777:g.24125del
LRG_777p1:p.Gln517Serfs
NC_000021.8:g.44476916del
NC_000021.8:g.44476917del
NM_000071.2:c.1548delC

Protein change:

Q412fs

Molecular consequence:

NM_000071.3:c.1549del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001178008.3:c.1549del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001178009.3:c.1549del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001320298.2:c.1549del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001321072.1:c.1234del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

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maturase, partial (mitochondrion) [Schizocodon soldanelloides]
maturase, partial (mitochondrion) [Schizocodon soldanelloides]
gi|20270854|gb|AAM18449.1|

Protein
maturase, partial (mitochondrion) [Symplocos sp. Chung and Anderberg 1351]
maturase, partial (mitochondrion) [Symplocos sp. Chung and Anderberg 1351]
gi|20270870|gb|AAM18457.1|

Protein
Mus musculus grainyhead like transcription factor 2 (Grhl2), mRNA
Mus musculus grainyhead like transcription factor 2 (Grhl2), mRNA
gi|274320613|ref|NM_026496.4|

Nucleotide
Profile neighbors for GEO Profiles (Select 44329154) (199)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 44328753) (19)
GEO Profiles

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003338717	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 15, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12815602, 21520339, 25044645, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003338717

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 15, 2022)

germline

clinical testing

PubMed (4)
[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

Identification and functional analyses of CBS alleles in Spanish and Argentinian homocystinuric patients.

Cozar M, Urreizti R, Vilarinho L, Grosso C, Dodelson de Kremer R, Asteggiano CG, Dalmau J, García AM, Vilaseca MA, Grinberg D, Balcells S.

Hum Mutat. 2011 Jul;32(7):835-42. doi: 10.1002/humu.21514. Epub 2011 Jun 7.

PubMed [citation]

PMID:: 21520339

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003338717.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Gln517Serfs*24) in the CBS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 35 amino acid(s) of the CBS protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CBS-related conditions. This variant disrupts a region of the CBS protein in which other variant(s) (p.Lys523Serfs*18) have been determined to be pathogenic (PMID: 12815602, 21520339, 25044645). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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

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