NM_000071.3(CBS):c.920G>T (p.Gly307Val) AND HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 29, 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:: RCV003494862.2

Allele description [Variation Report for NM_000071.3(CBS):c.920G>T (p.Gly307Val)]

NM_000071.3(CBS):c.920G>T (p.Gly307Val)

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.920G>T (p.Gly307Val)

HGVS:

NC_000021.9:g.43062987C>A
NG_008938.1:g.17944G>T
NM_000071.3:c.920G>TMANE SELECT
NM_001178008.3:c.920G>T
NM_001178009.3:c.920G>T
NM_001320298.2:c.920G>T
NM_001321072.1:c.605G>T
NP_000062.1:p.Gly307Val
NP_000062.1:p.Gly307Val
NP_001171479.1:p.Gly307Val
NP_001171480.1:p.Gly307Val
NP_001307227.1:p.Gly307Val
NP_001308001.1:p.Gly202Val
LRG_777t1:c.920G>T
LRG_777:g.17944G>T
LRG_777p1:p.Gly307Val
NC_000021.8:g.44483097C>A
NM_000071.2:c.920G>T

Protein change:

G202V

Molecular consequence:

NM_000071.3:c.920G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001178008.3:c.920G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001178009.3:c.920G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001320298.2:c.920G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001321072.1:c.605G>T - 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
SCV004368860	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 29, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 7506602, 7581402, 8744616, 9889017, 20506325, 22267502, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004368860

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 29, 2022)

germline

clinical testing

PubMed (7)
[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

Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria.

Hu FL, Gu Z, Kozich V, Kraus JP, Ramesh V, Shih VE.

Hum Mol Genet. 1993 Nov;2(11):1857-60.

PubMed [citation]

PMID:: 7506602

High frequency (71%) of cystathionine beta-synthase mutation G307S in Irish homocystinuria patients.

Gallagher PM, Ward P, Tan S, Naughten E, Kraus JP, Sellar GC, McConnell DJ, Graham I, Whitehead AS.

Hum Mutat. 1995;6(2):177-80. No abstract available.

PubMed [citation]

PMID:: 7581402

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004368860.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly307 amino acid residue in CBS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7506602, 7581402, 8744616, 9889017, 20506325, 22267502). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has not been reported in the literature in individuals affected with CBS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 307 of the CBS protein (p.Gly307Val).

#	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