VCV000029903.1 - ClinVar

NM_000361.3(THBD):c.1209G>T (p.Arg403Ser)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000361.3(THBD):c.1209G>T (p.Arg403Ser)

Variation ID: 29903 Accession: VCV000029903.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 20p11.21 20: 23048296 (GRCh38) [ NCBI UCSC ] 20: 23028933 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	Apr 4, 2013	May 15, 2002

HGVS

Nucleotide	Protein	Molecular consequence
NM_000361.3:c.1209G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000352.1:p.Arg403Ser	missense
NC_000020.11:g.23048296C>A
NC_000020.10:g.23028933C>A
NG_012027.1:g.6369G>T
LRG_168:g.6369G>T
LRG_168t1:c.1209G>T	LRG_168p1:p.Arg403Ser

... more HGVS ... less HGVS

Protein change

R403S

Other names

R385S

Canonical SPDI

NC_000020.11:23048295:C:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00001

Links

ClinGen: CA128733 OMIM: 188040.0009 dbSNP: rs398122807 VarSome

Comment on variant

NCBI staff reviewed the sequence information reported in PubMed 11986219 to determine the location of this allele on the current reference sequence. The amino acid numbering of the mature processed protein used in the citation differs from the native translation by 18 residues (i.e., Arg403 native is Arg385 processed).

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
THBD		-	-	GRCh38 GRCh37	450	472

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Thrombomodulin-related bleeding disorder	Pathogenic (1)	no assertion criteria provided	May 15, 2002	RCV000022787.24

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (May 15, 2002)	no assertion criteria provided Method: literature only	THROMBOPHILIA DUE TO THROMBOMODULIN DEFECT Affected status: not provided Allele origin: germline	OMIM Accession: SCV000044076.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (1) PubMed: 11986219 Comment on evidence: In a woman with recurrent deep venous thrombosis beginning at age 76 who had a myocardial infarction at age 90, Kunz et al. (2002) identified … (more) In a woman with recurrent deep venous thrombosis beginning at age 76 who had a myocardial infarction at age 90, Kunz et al. (2002) identified a heterozygous 1209G-T transversion in the THBD gene, resulting in an arg385-to-ser (R385S) substitution in the last amino acid in the fourth EGF-like domain, which is important for efficient protein C activation. In vitro functional expression studies showed that the mutant protein had reduced expression (50% compared to wildtype), as well as significantly decreased cofactor activity with increased Km values for protein C activation. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Naturally occurring mutations in the thrombomodulin gene leading to impaired expression and function.	Kunz G	Blood	2002	PMID: 11986219

Text-mined citations for rs398122807 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 08, 2024

ClinVar Genomic variation as it relates to human health

NM_000361.3(THBD):c.1209G>T (p.Arg403Ser)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs398122807 ...