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NM_000071.3(CBS):c.341C>T (p.Ala114Val) AND HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 30, 2024
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:
RCV002227956.5

Allele description

NM_000071.3(CBS):c.341C>T (p.Ala114Val)

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.341C>T (p.Ala114Val)
Other names:
p.A114V:GCG>GTG
HGVS:
  • NC_000021.9:g.43066353G>A
  • NG_008938.1:g.14578C>T
  • NM_000071.3:c.341C>TMANE SELECT
  • NM_001178008.3:c.341C>T
  • NM_001178009.3:c.341C>T
  • NM_001320298.2:c.341C>T
  • NM_001321072.1:c.26C>T
  • NP_000062.1:p.Ala114Val
  • NP_000062.1:p.Ala114Val
  • NP_001171479.1:p.Ala114Val
  • NP_001171480.1:p.Ala114Val
  • NP_001307227.1:p.Ala114Val
  • NP_001308001.1:p.Ala9Val
  • LRG_777t1:c.341C>T
  • LRG_777:g.14578C>T
  • LRG_777p1:p.Ala114Val
  • NC_000021.8:g.44486463G>A
  • NM_000071.2:c.341C>T
  • P35520:p.Ala114Val
Protein change:
A114V; ALA114VAL
Links:
UniProtKB: P35520#VAR_002174; OMIM: 613381.0003; dbSNP: rs121964964
NCBI 1000 Genomes Browser:
rs121964964
Molecular consequence:
  • NM_000071.3:c.341C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178008.3:c.341C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178009.3:c.341C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320298.2:c.341C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001321072.1:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000956328Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 30, 2024) 		germlineclinical testing

PubMed (8)
[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

The molecular basis of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of four novel mutations.

Sebastio G, Sperandeo MP, Panico M, de Franchis R, Kraus JP, Andria G.

Am J Hum Genet. 1995 Jun;56(6):1324-33.

PubMed [citation]
PMID:
7762555
PMCID:
PMC1801112

Molecular defect in a patient with pyridoxine-responsive homocystinuria.

Kozich V, de Franchis R, Kraus JP.

Hum Mol Genet. 1993 Jun;2(6):815-6. No abstract available.

PubMed [citation]
PMID:
8353501
See all PubMed Citations (8)

Details of each submission

From Invitae, SCV000956328.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 114 of the CBS protein (p.Ala114Val). This variant is present in population databases (rs121964964, gnomAD 0.03%). This missense change has been observed in individual(s) with homocystinuria due to cystathionine-beta synthase (CBS) deficiency (PMID: 7762555, 8353501). ClinVar contains an entry for this variant (Variation ID: 119). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CBS function (PMID: 20490928, 20506325, 22069143, 22267502, 22612060). 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 16, 2024