NM_000071.3(CBS):c.727C>T (p.Gln243Ter) AND HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 5, 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:: RCV003495344.2

Allele description [Variation Report for NM_000071.3(CBS):c.727C>T (p.Gln243Ter)]

NM_000071.3(CBS):c.727C>T (p.Gln243Ter)

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.727C>T (p.Gln243Ter)

HGVS:

NC_000021.9:g.43065212G>A
NG_008938.1:g.15719C>T
NM_000071.3:c.727C>TMANE SELECT
NM_001178008.3:c.727C>T
NM_001178009.3:c.727C>T
NM_001320298.2:c.727C>T
NM_001321072.1:c.412C>T
NP_000062.1:p.Gln243Ter
NP_000062.1:p.Gln243Ter
NP_001171479.1:p.Gln243Ter
NP_001171480.1:p.Gln243Ter
NP_001307227.1:p.Gln243Ter
NP_001308001.1:p.Gln138Ter
LRG_777t1:c.727C>T
LRG_777:g.15719C>T
LRG_777p1:p.Gln243Ter
NC_000021.8:g.44485322G>A
NM_000071.2:c.727C>T

Protein change:

Q138*

Molecular consequence:

NM_000071.3:c.727C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001178008.3:c.727C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001178009.3:c.727C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001320298.2:c.727C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001321072.1:c.412C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Carnivore fecal samples
Carnivore fecal samples
Understanding predator guild niche partitioning using DNA metabarcoding

BioProject

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
SCV004297410	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 5, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10338090, 12124992, 14972327, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004297410

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 5, 2023)

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

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

The molecular basis of cystathionine beta-synthase deficiency in Australian patients: genotype-phenotype correlations and response to treatment.

Gaustadnes M, Wilcken B, Oliveriusova J, McGill J, Fletcher J, Kraus JP, Wilcken DE.

Hum Mutat. 2002 Aug;20(2):117-26.

PubMed [citation]

PMID:: 12124992

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297410.1

#	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.Gln243*) in the CBS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CBS are known to be pathogenic (PMID: 10338090, 12124992). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with homocystinuria (PMID: 14972327). 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