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NM_000071.3(CBS):c.1007G>C (p.Arg336Pro) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 4, 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:
RCV002420789.2

Allele description [Variation Report for NM_000071.3(CBS):c.1007G>C (p.Arg336Pro)]

NM_000071.3(CBS):c.1007G>C (p.Arg336Pro)

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.1007G>C (p.Arg336Pro)
HGVS:
  • NC_000021.9:g.43062343C>G
  • NG_008938.1:g.18588G>C
  • NM_000071.3:c.1007G>CMANE SELECT
  • NM_001178008.3:c.1007G>C
  • NM_001178009.3:c.1007G>C
  • NM_001320298.2:c.1007G>C
  • NM_001321072.1:c.692G>C
  • NP_000062.1:p.Arg336Pro
  • NP_001171479.1:p.Arg336Pro
  • NP_001171480.1:p.Arg336Pro
  • NP_001307227.1:p.Arg336Pro
  • NP_001308001.1:p.Arg231Pro
  • LRG_777:g.18588G>C
  • NC_000021.8:g.44482453C>G
  • NM_000071.2:c.1007G>C
Protein change:
R231P
Links:
dbSNP: rs760417941
NCBI 1000 Genomes Browser:
rs760417941
Molecular consequence:
  • NM_000071.3:c.1007G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178008.3:c.1007G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178009.3:c.1007G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320298.2:c.1007G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001321072.1:c.692G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:
Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:
MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002725410Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Aug 4, 2022) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Ambry Genetics, SCV002725410.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.R336P variant (also known as c.1007G>C), located in coding exon 9 of the CBS gene, results from a G to C substitution at nucleotide position 1007. The arginine at codon 336 is replaced by proline, an amino acid with dissimilar properties. This alteration has been reported as compound heterozygous with a known pathogenic mutation in CBS in an individual with homocystinuria (Ambry internal data). Another alteration at the same codon, p.R336H (c.1007G>A), has been detected as homozygous in two family members with homocystinuria (Coudé M et al. J Inherit Metab Dis, 1998 Dec;21:823-8), and showed an impact on enzyme activity in functional studies (Urreizti R et al. Hum Mutat, 2006 Feb;27:211; Mayfield JA et al. Genetics, 2012 Apr;190:1309-23; Mendes MI et al. Hum Mol Genet, 2015 Dec;24:7339-48). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Sep 29, 2024