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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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003338717Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 15, 2022) 		germlineclinical testing

PubMed (4)
[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

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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

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

Last Updated: Sep 29, 2024