NM_000128.4(F11):c.1234C>T (p.Gln412Ter) AND Hereditary factor XI deficiency disease

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: May 25, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000670354.7

Allele description [Variation Report for NM_000128.4(F11):c.1234C>T (p.Gln412Ter)]

NM_000128.4(F11):c.1234C>T (p.Gln412Ter)

Gene:

F11:coagulation factor XI [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q35.2

Genomic location:

Preferred name:

NM_000128.4(F11):c.1234C>T (p.Gln412Ter)

HGVS:

NC_000004.12:g.186284190C>T
NG_008051.1:g.23227C>T
NM_000128.4:c.1234C>TMANE SELECT
NP_000119.1:p.Gln412Ter
NP_000119.1:p.Gln412Ter
LRG_583t1:c.1234C>T
LRG_583:g.23227C>T
LRG_583p1:p.Gln412Ter
NC_000004.11:g.187205344C>T
NM_000128.3:c.1234C>T

Protein change:

Q412*

Links:

dbSNP: rs538083600

NCBI 1000 Genomes Browser:

rs538083600

Molecular consequence:

NM_000128.4:c.1234C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary factor XI deficiency disease
Synonyms:: Plasma thromboplastin antecedent deficiency; PTA deficiency; Rosenthal syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012897; MeSH: D005173; MedGen: C0015523; Orphanet: 329; OMIM: 612416

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000795196	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Oct 31, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000893675	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 31, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004175862	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 1, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004238183	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 25, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical and molecular epidemiology of factor XI deficiency in India.

Kawankar N, Rathi J, Ghosh K, Shetty S.

Thromb Res. 2016 Nov;147:85-87. doi: 10.1016/j.thromres.2016.09.022. Epub 2016 Sep 21. No abstract available.

PubMed [citation]

PMID:: 27710856

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

PMC

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From Counsyl, SCV000795196.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV000893675.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV004175862.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The stop gained c.1234C>T(p.Gln412Ter) variant in F11 gene has been reported previously in homozygous state in an individual affected with factor XI deficiency (Kawankar N, et. al., 2016). The c.1234C>T variant is novel (not in any individuals) in gnomAD Exomes. This variant has been reported to the ClinVar database as Likely Pathogenic / Pathogenic. The nucleotide change c.1234C>T in F11 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This sequence change creates a premature translational stop signal (p.Gln412Ter) in the F11 gene. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants in F11 gene have been previously reported to be pathogenic (Duga S & Salomon O., 2013). However, additional functional studies will be required to prove the pathogenicity of this variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV004238183.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 6, 2024

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