U.S. flag

An official website of the United States government

NM_000071.3(CBS):c.362G>A (p.Arg121His) AND Homocystinuria

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 31, 2020
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:
RCV001192720.2

Allele description [Variation Report for NM_000071.3(CBS):c.362G>A (p.Arg121His)]

NM_000071.3(CBS):c.362G>A (p.Arg121His)

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.362G>A (p.Arg121His)
HGVS:
  • NC_000021.9:g.43066332C>T
  • NG_008938.1:g.14599G>A
  • NM_000071.3:c.362G>AMANE SELECT
  • NM_001178008.3:c.362G>A
  • NM_001178009.3:c.362G>A
  • NM_001320298.2:c.362G>A
  • NM_001321072.1:c.47G>A
  • NP_000062.1:p.Arg121His
  • NP_000062.1:p.Arg121His
  • NP_001171479.1:p.Arg121His
  • NP_001171480.1:p.Arg121His
  • NP_001307227.1:p.Arg121His
  • NP_001308001.1:p.Arg16His
  • LRG_777t1:c.362G>A
  • LRG_777:g.14599G>A
  • LRG_777p1:p.Arg121His
  • NC_000021.8:g.44486442C>T
  • NM_000071.2:c.362G>A
  • P35520:p.Arg121His
Protein change:
R121H
Links:
UniProtKB: P35520#VAR_008055; dbSNP: rs770095972
NCBI 1000 Genomes Browser:
rs770095972
Molecular consequence:
  • NM_000071.3:c.362G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178008.3:c.362G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178009.3:c.362G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320298.2:c.362G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001321072.1:c.47G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Homocystinuria
Identifiers:
MONDO: MONDO:0004737; MedGen: C0019880; Human Phenotype Ontology: HP:0002156

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001361015Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Aug 31, 2020) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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 p.T191M mutation of the CBS gene is highly prevalent among homocystinuric patients from Spain, Portugal and South America.

Urreizti R, Asteggiano C, Bermudez M, Córdoba A, Szlago M, Grosso C, de Kremer RD, Vilarinho L, D'Almeida V, Martínez-Pardo M, Peña-Quintana L, Dalmau J, Bernal J, Briceño I, Couce ML, Rodés M, Vilaseca MA, Balcells S, Grinberg D.

J Hum Genet. 2006;51(4):305-313. doi: 10.1007/s10038-006-0362-0. Epub 2006 Feb 15. Erratum in: J Hum Genet. 2007;52(4):388-9. Szlago, Mariana [corrected to Szlago, Marina]. J Hum Genet. 2007 Apr;52(4):388-389. doi: 10.1007/s10038-006-0103-4.

PubMed [citation]
PMID:
16479318
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361015.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: CBS c.362G>A (p.Arg121His) results in a non-conservative amino acid change located in the Pyridoxal-phosphate dependent enzyme domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251070 control chromosomes. c.362G>A has been reported in the literature in multiple individuals affected with Homocystinuria (example, Katsushima_2006, Urreizti_2006, Kraus_1999). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in severely impaired enzyme activity resulting from impaired tetramer assembly (Katsushima_2006). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Sep 29, 2024