NM_000071.3(CBS):c.476_477insCAGGGCCC (p.Val160fs) AND HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 9, 2019
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:: RCV002241644.12

Allele description [Variation Report for NM_000071.3(CBS):c.476_477insCAGGGCCC (p.Val160fs)]

NM_000071.3(CBS):c.476_477insCAGGGCCC (p.Val160fs)

Gene:

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

Variant type:

Insertion

Cytogenetic location:

21q22.3

Genomic location:

Preferred name:

NM_000071.3(CBS):c.476_477insCAGGGCCC (p.Val160fs)

HGVS:

NC_000021.9:g.43065671_43065672insGGCCCTGG
NG_008938.1:g.15260_15261insCAGGGCCC
NM_000071.3:c.476_477insCAGGGCCCMANE SELECT
NM_001178008.3:c.476_477insCAGGGCCC
NM_001178009.3:c.476_477insCAGGGCCC
NM_001320298.2:c.476_477insCAGGGCCC
NM_001321072.1:c.161_162insCAGGGCCC
NP_000062.1:p.Val160fs
NP_001171479.1:p.Val160fs
NP_001171480.1:p.Val160fs
NP_001307227.1:p.Val160fs
NP_001308001.1:p.Val55fs
LRG_777t1:c.476_477insCAGGGCCC
LRG_777:g.15260_15261insCAGGGCCC
NC_000021.8:g.44485780_44485781insGGGCCCTG
NC_000021.8:g.44485781_44485782insGGCCCTGG
NM_000071.2:c.476_477insCAGGGCCC

Protein change:

V160fs

Links:

dbSNP: rs1982618780

NCBI 1000 Genomes Browser:

rs1982618780

Molecular consequence:

NM_000071.3:c.476_477insCAGGGCCC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001178008.3:c.476_477insCAGGGCCC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001178009.3:c.476_477insCAGGGCCC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001320298.2:c.476_477insCAGGGCCC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001321072.1:c.161_162insCAGGGCCC - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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Homo sapiens centrosomal protein 70kDa, mRNA (cDNA clone MGC:26763 IMAGE:4829481...
Homo sapiens centrosomal protein 70kDa, mRNA (cDNA clone MGC:26763 IMAGE:4829481), complete cds
gi|34190393|gb|BC030598.2|

Nucleotide
FCSK [Crocodylus porosus]
FCSK [Crocodylus porosus]
Gene ID:109310453

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001422081	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 9, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10338090, 12124992, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001422081

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 9, 2019)

germline

clinical testing

PubMed (3)
[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 (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001422081.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CBS are known to be pathogenic (PMID: 10338090, 12124992). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with CBS-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val160Argfs*4) in the CBS gene. It is expected to result in an absent or disrupted protein product.

#	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: Oct 13, 2024

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