NM_000128.4(F11):c.1772G>A (p.Gly591Asp) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 18, 2023
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:: RCV003576286.2

Allele description [Variation Report for NM_000128.4(F11):c.1772G>A (p.Gly591Asp)]

NM_000128.4(F11):c.1772G>A (p.Gly591Asp)

Genes:

F11-AS1:F11 antisense RNA 1 [Gene - HGNC]
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.1772G>A (p.Gly591Asp)

HGVS:

NC_000004.12:g.186288508G>A
NG_008051.1:g.27545G>A
NM_000128.4:c.1772G>AMANE SELECT
NP_000119.1:p.Gly591Asp
NP_000119.1:p.Gly591Asp
LRG_583t1:c.1772G>A
LRG_583:g.27545G>A
LRG_583p1:p.Gly591Asp
NC_000004.11:g.187209662G>A
NM_000128.3:c.1772G>A
NR_033900.1:n.986C>T

Protein change:

G591D

Molecular consequence:

NM_000128.4:c.1772G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_033900.1:n.986C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004329367	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 18, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29325334, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004329367

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 18, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

[Analysis on the novel compound heterozygous mutation FⅪ of a patient with hereditary factor Ⅺ deficiency].

Xu K, Shu KY, Li FF, Chen T, Liu J, Jin SS, Guo JJ, Zhang ZH, Jiang MH.

Zhonghua Yi Xue Za Zhi. 2017 Dec 26;97(48):3774-3778. doi: 10.3760/cma.j.issn.0376-2491.2017.48.004. Chinese.

PubMed [citation]

PMID:: 29325334

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004329367.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 591 of the F11 protein (p.Gly591Asp). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt F11 protein function. This variant is also known as c.1815G>A (p.Gly573Asp). This missense change has been observed in individual(s) with autosomal recessive factor XI deficiency (PMID: 29325334). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals.

#	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: Sep 29, 2024

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