NM_000071.3(CBS):c.683A>G (p.Asn228Ser) AND Classic homocystinuria

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Sep 14, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000669206.5

Allele description [Variation Report for NM_000071.3(CBS):c.683A>G (p.Asn228Ser)]

NM_000071.3(CBS):c.683A>G (p.Asn228Ser)

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.683A>G (p.Asn228Ser)

HGVS:

NC_000021.9:g.43065256T>C
NG_008938.1:g.15675A>G
NM_000071.3:c.683A>GMANE SELECT
NM_001178008.3:c.683A>G
NM_001178009.3:c.683A>G
NM_001320298.2:c.683A>G
NM_001321072.1:c.368A>G
NP_000062.1:p.Asn228Ser
NP_000062.1:p.Asn228Ser
NP_001171479.1:p.Asn228Ser
NP_001171480.1:p.Asn228Ser
NP_001307227.1:p.Asn228Ser
NP_001308001.1:p.Asn123Ser
LRG_777t1:c.683A>G
LRG_777:g.15675A>G
LRG_777p1:p.Asn228Ser
NC_000021.8:g.44485366T>C
NM_000071.2:c.683A>G

Protein change:

N123S

Links:

dbSNP: rs1555874803

NCBI 1000 Genomes Browser:

rs1555874803

Molecular consequence:

NM_000071.3:c.683A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001178008.3:c.683A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001178009.3:c.683A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001320298.2:c.683A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001321072.1:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Classic homocystinuria
Synonyms:: HOMOCYSTINURIA WITH OR WITHOUT RESPONSE TO PYRIDOXINE; Homocystinuria due to CBS deficiency; Homocystinuria due to cystathionine beta-synthase deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009352; MedGen: C0751202; Orphanet: 394; OMIM: 236200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000793935	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Sep 12, 2017)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 20066033, 22267502, 14635102, 12686134, 17540596, 20455263 Citation Link,
SCV004213868	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 14, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000793935

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Sep 12, 2017)

unknown

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link,

SCV004213868

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 14, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Activation of mutant enzyme function in vivo by proteasome inhibitors and treatments that induce Hsp70.

Singh LR, Gupta S, Honig NH, Kraus JP, Kruger WD.

PLoS Genet. 2010 Jan;6(1):e1000807. doi: 10.1371/journal.pgen.1000807. Epub 2010 Jan 8.

PubMed [citation]

PMID:: 20066033
PMCID:: PMC2795852

Surrogate genetics and metabolic profiling for characterization of human disease alleles.

Mayfield JA, Davies MW, Dimster-Denk D, Pleskac N, McCarthy S, Boydston EA, Fink L, Lin XX, Narain AS, Meighan M, Rine J.

Genetics. 2012 Apr;190(4):1309-23. doi: 10.1534/genetics.111.137471. Epub 2012 Jan 20. Erratum in: Genetics. 2012 Oct;192(2):759-60.

PubMed [citation]

PMID:: 22267502
PMCID:: PMC3316645

See all PubMed Citations (7)

Details of each submission

From Counsyl, SCV000793935.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004213868.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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