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NM_000071.3(CBS):c.969G>A (p.Trp323Ter) AND HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 6, 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:
RCV003495115.1

Allele description [Variation Report for NM_000071.3(CBS):c.969G>A (p.Trp323Ter)]

NM_000071.3(CBS):c.969G>A (p.Trp323Ter)

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.969G>A (p.Trp323Ter)
Other names:
p.W323*:TGG>TGA
HGVS:
  • NC_000021.9:g.43062381C>T
  • NG_008938.1:g.18550G>A
  • NM_000071.3:c.969G>AMANE SELECT
  • NM_001178008.2:c.969G>A
  • NM_001178008.3:c.969G>A
  • NM_001178009.3:c.969G>A
  • NM_001320298.2:c.969G>A
  • NM_001321072.1:c.654G>A
  • NP_000062.1:p.Trp323Ter
  • NP_000062.1:p.Trp323Ter
  • NP_001171479.1:p.Trp323Ter
  • NP_001171480.1:p.Trp323Ter
  • NP_001307227.1:p.Trp323Ter
  • NP_001308001.1:p.Trp218Ter
  • LRG_777t1:c.969G>A
  • LRG_777:g.18550G>A
  • LRG_777p1:p.Trp323Ter
  • NC_000021.8:g.44482491C>T
  • NM_000071.2:c.969G>A
  • NM_001178009.2:c.969G>A
Protein change:
W218*
Links:
dbSNP: rs863223432
NCBI 1000 Genomes Browser:
rs863223432
Molecular consequence:
  • NM_000071.3:c.969G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001178008.3:c.969G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001178009.3:c.969G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001320298.2:c.969G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001321072.1:c.654G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004297406Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 6, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 (5)

Details of each submission

From Invitae, SCV004297406.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Trp323*) 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 present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with homocystinuria (PMID: 21517828, 29352562). ClinVar contains an entry for this variant (Variation ID: 212856). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 6, 2024