VCV000001164.2 - ClinVar

NM_000505.4(F12):c.1768T>A (p.Cys590Ser)

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_000505.4(F12):c.1768T>A (p.Cys590Ser)

Variation ID: 1164 Accession: VCV000001164.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q35.3 5: 177402372 (GRCh38) [ NCBI UCSC ] 5: 176829373 (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	Aug 8, 2019	Aug 8, 2019	Nov 1, 1989

HGVS

Nucleotide	Protein	Molecular consequence
NM_000505.4:c.1768T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000496.2:p.Cys590Ser	missense
NC_000005.10:g.177402372A>T
NC_000005.9:g.176829373A>T
NG_007568.1:g.12205T>A
LRG_145:g.12205T>A
LRG_145t1:c.1768T>A	LRG_145p1:p.Cys590Ser

... more HGVS ... less HGVS

Protein change

C590S

Other names

F12, CYS571SER
C571S

Canonical SPDI

NC_000005.10:177402371:A:T

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.

Trans-Omics for Precision Medicine (TOPMed) 0.00000

The Genome Aggregation Database (gnomAD) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00001

Links

OMIM: 610619.0001 dbSNP: rs1157280571 VarSome

Comment on variant

ClinGen staff contributed the HGVS expression for this variant.

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.
F12		-	-	GRCh38 GRCh37	158	239
SLC34A1		-	-	GRCh38 GRCh37	385	467

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.
FACTOR XII (WASHINGTON D.C.)	Pathogenic (1)	no assertion criteria provided	Nov 1, 1989	RCV000001223.4

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 (Nov 01, 1989)	no assertion criteria provided Method: literature only	FACTOR XII (WASHINGTON D.C.) Affected status: not provided Allele origin: germline	OMIM Accession: SCV000021373.3 First in ClinVar: Apr 04, 2013 Last updated: Aug 08, 2019	Publications: PubMed (1) PubMed: 2510163 Comment on evidence: Miyata et al. (1989) demonstrated that the functional impairment of factor XII (Washington D.C.) (234000) is due to replacement of cys571 with serine in the … (more) Miyata et al. (1989) demonstrated that the functional impairment of factor XII (Washington D.C.) (234000) is due to replacement of cys571 with serine in the catalytic domain. This mutation has also been referred to as CYS590SER (C590S). (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
Coagulation factor XII (Hageman factor) Washington D.C.: inactive factor XIIa results from Cys-571----Ser substitution.	Miyata T	Proceedings of the National Academy of Sciences of the United States of America	1989	PMID: 2510163

Text-mined citations for rs1157280571 ...

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 Apr 25, 2022

ClinVar Genomic variation as it relates to human health

NM_000505.4(F12):c.1768T>A (p.Cys590Ser)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1157280571 ...